By Riëtte van Laack –

The Eastern District Court of California enjoined California from enforcing California's Penal Code Section 599f against federally inspected swine slaughterhouses on the ground that section 599f is expressly preempted by the Federal Meat Inspection Act (“FMIA”). 

Section 599f prohibits a slaughterhouse from buying, selling or receiving nonambulatory animals for human consumption, and requires that any nonambulatory animal be euthanized immediately.  In contrast, the FMIA and its implementing regulations allow slaughterhouses to set aside disabled or fatigued animals (other than cattle) for inspection. 

The FMIA contains an express preemption clause specifically limiting the states in their ability to govern meat inspection and labeling requirements of any federally inspected establishment. 21 U.S.C. § 678.  The preemption clause does not limit states from regulating what types of meat may be sold for human consumption.

Section 599f would alter the federally mandated procedure for nonambulatory animals.  Because that section’s prohibition “differs from” and is “in addition” to FMIA requirements, the Court held that the section is expressly preempted by the FMIA.  California argued that Section 599f did not impose additional inspection requirements, but rather regulated the “type of meat” which may be sold for human consumption in California.  The Court summarily dismissed this argument because a “nonambulatory pig” is not “type of meat.”  Moreover, the Court found that the FMIA ensures the safety of meat and protects the health of the consumers, including California’s citizens.

By Cassandra A. Soltis –

A settlement agreement reached between numerous state attorneys general and Coke, Nestle, and Beverage Partnership Worldwide makes clear that it is not just the Federal Trade Commission that is scrutinizing weight loss claims.  The target of the attorneys general action is Enviga, a green tea beverage that is touted as having “negative calories,” meaning that calories are burned by simply drinking the product.  Marketing for Enviga also implied that users of the product will lose weight.  As part of the settlement agreement, whenever “negative calories” or similar claims are used in the marketing of either Enviga or any “similarly formulated product,” the companies must make clear that weight loss cannot be achieved absent diet and exercise.   

As support for the “proven” negative calorie claims, the companies cite to a small study on healthy individuals that lasted only three days.  The study subjects, whose ages ranged from 28-35 years old, were in the normal weight range.  Although some study participants burned additional calories by drinking 3 cans of Enviga per day, none experienced weight loss.  Furthermore, the study did not find that the calorie-burning effect could be maintained for an indefinite period. 

The companies will pay $650,000 to the states.  The Franklin Circuit Court will review the final settlement documents for approval.  For more information, see the press release from the Attorney General of Kentucky here.

By Susan Matthees and Jeff Wasserstein –

Although the stimulus bill that President Obama recently signed into law received significant attention for its economic implications, less noticed was Title XIII of the stimulus bill, entitled the "Health Information Technology for Economic and Clinical Health Act" or the "HITECH Act."  The HITECH Act includes a provision related to the HIPAA Privacy Standards that will restrict certain communications made by pharmacies and other providers relating to pharmaceutical products.

Prior to the HITECH Act, communications made by pharmacies or other providers to recommend alternative treatments or therapies or to recommend refilling prescriptions were considered to be communications for the purposes of "health care operations" and thus were permitted without patient authorization, even if a third party was funding the communication.  Thus, a manufacturer could without a patient authorization pay a doctor or pharmacy to send prescription refill reminders to patients as well as pay a doctor or pharmacy to recommend an alternative medication – see HIPAA Frequent Questions.  However, the HITECH Act limits marketing that is based on protected health information.  Under the HITECH Act, if a third party is paying for the communication, absent an authorization a pharmacy or provider can only send such a communication to a patient who has already been prescribed the drug or biologic.  Thus, manufacturers can continue to pay for refill reminders, but not for alternative drug recommendations.  This limitation applies to covered entities and business associates, and thus would apply to pharmacies, physicians, health plans, as well as pharmacy benefit managers.

The Act also will also change liability for business associates.  Business associates contract with entities that must comply with the HIPAA Privacy Standards to provide services on behalf of the covered entity.  Prior to the stimulus bill, business associates were not liable under the civil or criminal penalty provisions of HIPAA, and were only liable for breach of contract (the business associate agreement) if they violated the provisions of the contract.  However, the HITECH Act makes business associates directly subject to HIPAA enforcement.

Pharmaceutical companies should take careful note of these new provisions, as it may significantly impact their marketing practices.  These provisions go into effect 12 months from the signing of the stimulus package, or February 17, 2010.

By Douglas B. Farquhar –      

More than nine years after passage of federal legislation that would permit individuals to legally import prescription drugs from Canada, the Obama Administration appears ready to open the door to importation.  Prior administrations, including President Clinton’s, prevented individuals from legally importing prescription drugs.  We briefly mentioned this development in a recent post on President Obama’s proposed budget, but we felt it deserved more detailed attention.

The Federal Food, Drug, and Cosmetic Act (“FDC Act”) generally prohibits importation of drugs by individuals, and explicitly prohibits the reimportation of drugs manufactured in the United States by individuals or entities other than manufacturers.  In the 1990’s, numerous individuals in the United States began importing prescription drugs (meaning finished products, as opposed to Active Pharmaceutical Ingredients) from Canada, by traveling to Canada and purchasing drugs in pharmacies there, or by mail order, either through Internet websites or through telephone purchases.  Several store-front operations opened in cities across the United States.  The stores facilitated these transactions by accepting prescriptions from customers and then arranging for the prescriptions to be filled by linked Canadian pharmacies and shipped to customers.  Individuals in the United States tend to import brand-name drugs, rather than generics, because the prices of generic drugs in the United States are favorable compared to those in Canada, while many brand-name drugs are much less expensive in Canada than in the United States.  FDA initiated legal action against one chain of these storefront operations (Rx Depot), and successfully sought an injunction shutting down the store and securing financial penalties against it.

In 2000, Congress, as part of the appropriations bill for FDA, included a provision allowing personal importation of prescription drugs if the Secretary of Health and Human Services (acting on behalf of FDA) demonstrated that “reimportation poses no additional risk to the public’s health and safety.”  Likewise, in the 2003 Medicare Prescription Drug, Improvement, and Modernization Act, a provision was enacted that required a system to be created for importation of prescription drugs from Canada, upon certification of safety and cost savings.  The provisions, codified in Section 804 of the FDC Act, are only effective if the Secretary of Health and Human Services (who has authority over FDA) certifies safety.

FDA has long opposed permitting individual imports of prescription drugs except under very limited conditions that do not include drugs which are approved for use in the United States.  Successive Secretaries of HHS have decided, therefore, that adequate protections of safety are not possible.

However, the recent budget proposal for FDA issued by the Obama Administration states that the budget “supports the Food and Drug Administration’s (FDA’s) new efforts to allow Americans to buy safe and effective drugs from other countries.”  Apparently, this is a reference to Section 804’s provisions, and may signal that officials appointed by President Obama are willing to open the gates to legal importation of drugs from Canada.

By Kurt R. Karst –     

Actavis Elizabeth LLC (“Actavis”) has sued FDA after the Agency refused to accept the company’s ANDA for a generic version of the ADHD drug VYVANSE (lisdexamfetamine dimesylate) Capsules earlier this year.  FDA’s Orange Book shows that VYVANSE is a Type 1 new molecular entity covered by a period of 5-year New Chemical Entity (“NCE”) exclusivity, as well as another period of 3-year exclusivity and two patents scheduled to expire on June 29, 2023.  The VYVANSE labeling states that the drug product is a therapeutically inactive pro-drug that is metabolically converted to dextroamphetamine, a previously approved drug (e.g., ADDERALL).  According to the Actavis complaint, which was filed in the U.S. District Court for the District of Columbia, the company submitted an ANDA containing a Paragraph IV certification to FDA on January 28, 2009, and on February 6, 2009, FDA informed Actavis that the Agency refused to file the ANDA in light of FDA’s award of NCE exclusivity for VYVANSE.

Actavis is effectively challenging FDA’s policy on the availability of NCE exclusivity for metabolically converted drugs.  FDA stated in the preamble to the Agency’s 1989 proposed regulations implementing the Hatch-Waxman Amendments that:

A compound (other than an ester) that requires metabolic conversion to produce an already approved active moiety is considered a “new molecular entity,” . . . and will be considered a new chemical entity entitled to 5 years of exclusivity.  FDA will consider whether a drug contains a previously approved active moiety on a case-by-case basis.

FDA, Proposed Rule, ANDA Regulations, 54 Fed. Reg. 28,872, 28,898 (July 10, 1989). 

Actavis argues that FDA should not have granted 5-year NCE exclusivity for VYVANSE, and that “FDA’s blanket distinction between covalent derivatives and non-covalent derivatives for purposes of awarding NCE exclusivity is inconsistent with the FDCA, its legislative history and FDA’s own regulations.”  Actavis’ complaint requests that the court: (1) enter judgment declaring that FDA’s grant of NCE exclusivity for VYVANSE and refusal to accept the company’s ANDA is arbitrary, capricious and contrary to law; and (2) enter an injunction directing FDA to rescind the VYVANSE 5-year exclusivity and accept the Actavis ANDA as of January 28, 2009.   

By Alan M. Kirschenbaum –

Last week we reported on the Obama Administration’s 10-year budget proposal, focusing on the Department of Health and Human Services budget.  As noted, the budget establishes a reserve fund of over $630 billion over 10 years to finance health care reform. 

$316 billion of this reserve fund would be financed by health care savings, some of which would result from significant changes in the regulatory landscape for prescription drugs.  First, under the Medicaid Rebate Program, the minimum rebate for innovator drugs would increase from 15.1 percent to 22.1 percent of average manufacturer price (“AMP”).  Also, Medicaid rebates would be payable for drugs dispensed by Medicaid managed care plans, which are currently exempt from rebates under the statute.

Second, a “regulatory, scientific, and legal pathway” would be established for the approval of generic biologicals.  The budget document assures that a period of exclusivity would be guaranteed for the innovator biological product, consistent with principles in the Hatch-Waxman provisions applicable to non-biological new drugs, but it does not indicate the proposed length of the exclusivity period.  Brand biological manufacturers would be prohibited from “ever-greening” – i.e., reformulating existing products in order to restart the exclusivity process.

Third, the budget "supports the Food and Drug Administration’s (FDA’s) new efforts to allow Americans to buy safe and effective drugs from other countries . . . ."  This cryptic statement appears to refer to the importation of finished pharmaceuticals, though the reference to FDA's "new efforts" is puzzling since FDA to date has prohibited such imports.  The budget does not provide any detail on what imports would be permitted, or how importation would be reconciled with FDA's efforts to "make . . . medical products safer" – – a goal identified in the very next sentence of the budget.

Fourth, drug companies would be prohibited from blocking the approval of generic drugs through anticompetitive agreements and collusion between brand name and generic drug manufacturers.  As we recently reported, such “pay for delay” arrangements are the subject of a recent Federal Trade Commission complaint and legislation introduced in the U.S. Senate. 

In addition to these drug-specific provisions, the reserve fund would be financed through savings from a number of payment reforms under Medicare and Medicaid, including reducing Medicare subsidies to Medicare Advantage plans by changing to a competitive system where payment is based on an average of plans’ submitted bids; reducing overpayments and fraud under Medicare (including Part D) and Medicaid; introducing pay-for-performance incentives into Medicare hospital inpatient payment; reducing hospital readmissions through incentives and penalties; and reforming the Medicare physician payment system to incentivize quality and efficiency.

By Kurt R. Karst –      

Over the past few weeks, we have posted (here and here) on citizen petitions submitted to FDA requesting that the Agency address whether the 30-month stay provisions of the Hatch-Waxman Amendments apply to a pending ANDA for a generic version of an old antibiotic drug, which ANDA contains a Paragraph IV certification to a patent listed in the Orange Book in accordance with § 4(b)(1) of the QI Program Supplemental Funding Act of 2008 (“QI Act”).  In the latest (third) citizen petition submitted to FDA concerning this issue, Hoffmann-La Roche and Roche Palo Alto LLC request that FDA address the issue with respect to another old antibiotic drug –  CELLCEPT (mycophenolate mofetil) Capsules and Tablets – for which U.S. Patent #4,753,935 was submitted to FDA for Orange Book listing in accordance with the QI Act.  Apotex reportedly submitted ANDAs (containing a Paragraph IV certification to the '935 patent) seeking approval for generic versions of Roche's CELLCEPT products and Roche sued Apotex within the statutory 45-day period.

Roche’s petition raises some of the same arguments raised in the previously submitted petitions concerning DORYX (doxycycline hyclate) Delayed-Release Tablets and SOLODYN (minocycline HCl) Extended Release Tablets; namely, that the plain language of the QI Act requires application of the 30-month stay provisions of the original Hatch-Waxman Amendments, rather than the version of the statute amended by the Medicare Modernization Act, which limits 30-month stays such that a generic applicant with a pending ANDA that amends its application to add a Paragraph IV certification to a later-listed patent is not subject to a 30-month stay in connection with that certification.  The Roche petition also argues that FDA should interpret the QI Act such that patents listed pursuant to QI Act § 4(b)(1) should be treated as having been filed with the original NDA, thus providing for 30-month stay availability.  Medicis makes a similar argument in the SOLODYN petition, but argues that patents covering old antibiotics listed in the Orange Book in accordance with QI Act § 4(b)(1) should be treated as having been filed in the original ANDA, instead of in an amendment.

Both Actavis and Teva have submitted comments requesting that the Agency deny such petitions and determine that a 30-month stay is not available. 

By Cassandra A. Soltis & Alan M. Kirschenbaum – 

Today the Obama Administration released a summary of its 10-year budget proposal  entitled “A New Era of Responsibility – Renewing America’s Promise.”  The document provides a high level outline of priorities – details reportedly will be released in April.  For FY 2010, the budget includes $76.8 billion for the Department of Health and Human Services (HHS).  Highlights of the HHS budget include the following:

• Health care reform:  The budget establishes a reserve fund of over $630 billion over 10 years to finance reform of the health care system to bring down costs and expand coverage.  The document acknowledges that this amount is a “down payment,” and additional funding will be needed to expand coverage to the uninsured.

• Lowering drug costs and improving safety of food and medical products:  The budget would establish a new regulatory pathway for generic biologics, and strengthen FDA’s efforts to ensure the safety of food and medical products, including those imported from other countries.  Over $1 billion will be included for FDA’s food safety efforts.

• Federal healthcare program integrity:  The Budget will dedicate additional resources to improve oversight and program integrity of the Medicare prescription drug benefit (Part D), Medicare Advantage, and Medicaid.  The Budget will also “strengthen[] the Medicare program by encouraging high quality and efficient care, and reducing excessive Medicare payments.”

• Medicare and Medicaid research agenda:  New funding will be allocated to demonstration and pilot projects to evaluate payment reforms, ways to provide higher quality care at lower cost, and beneficiary education.

• Comparative effectiveness research:  Building on the $1.1 billion included in the recently passed stimulus bill for comparative effectiveness research, the budget will continue to fund research comparing the effectiveness of medical treatments.  This, combined with electronic health records, will “distill[] all available evidence on the outcomes of different treatment options into user-friendly pop-up alerts for physicians at the point of care.”

• Cancer and AIDS:  Over $6 billion will be allocated to the National Institutes of Health for cancer research to develop innovative diagnostics and treatments for cancer.  Increased resources will also be devoted to the detection, prevention, and treatment of HIV/AIDS. 

By John R. Fleder, Douglas B. Farquhar & Ricardo Carvajal –

The U.S. Attorney for the Eastern District of California  (Sacramento) has announced guilty pleas by two individuals for fraudulent activities in connection with their distribution of tomato products.  Allegedly at the direction of her superiors at SK Foods L.P., one individual intentionally shipped products that were adulterated due to excessive mold, and falsified data in corresponding Certificates of Analysis.  She faces up to 3 years in prison.  A second individual employed by Frito-Lay, Inc. received $160,000 in bribes for steering contracts for food products to SK Foods.  He faces up to 20 years in prison.  Sentencing is scheduled for April 28.  There is no allegation that the affected products posed any health hazard to consumers.

By John R. Fleder, Douglas B. Farquhar & Ricardo Carvajal –

FDA has obtained summary judgment and an order of permanent injunction against a Minnesota seafood supplier that was found to have had an inadequate HACCP plan for more than three years, in violation of FDC Act § 402(a)(4) and 21 C.F.R. § 123.6(g).  However, the Court’s Opinion deals a severe blow to FDA’s consistent track record of seeking injunctions that are worded so as to allow FDA to decide by administrative edict that the defendant’s business must be shut down, after entry of the Injunction, if FDA believes the company has violated the Injunction.

When FDA and the Justice Department seek injunctions for FDC Act violations, they will frequently seek a partial or total shutdown of the allegedly offending defendant until it can come into compliance with applicable legal requirements.  In addition, the standard FDA Consent Decree (and litigated Decree) has provisions governing what occurs when FDA subsequently decides that the Decree has been violated.  The typical Decree allows FDA to shut down the allegedly offending company merely by sending the company a letter stating that the company has continued to violate the law.  Upon receipt of that letter, the firm is generally required to shutdown its operations, with very limited right to get review from a court of that shutdown demand.  This provision is referred to as “letter shutdown authority.”

In this case, although FDA sought letter shutdown authority, the Court turned the standard FDA provision on its head.  The Injunction entered by the judge provides that if FDA does not approve of the defendant’s HACCP plan, “and if the FDA wishes to prevent defendants from beginning to operate the proposed business covered by the plan, the FDA must bring” an entirely new enforcement action against the defendant.  Thus, unlike the typical Decree, FDA cannot simply shut down a defendant when FDA believes the firm is in violation of the Decree.  Instead, the government must file (and prevail in) a second lawsuit against the defendant.

As noted by the court, there is no allegation that the defendant’s products posed any health hazard to consumers.  The case is U.S. v. Captain’s Select Seafood, Inc., 2009 WL 398081 (D. Minn.).  FDA’s press release is available here.

By Kurt R. Karst –      

Earlier today, FDA announced that the Agency was taking the unusual step of invoking its Application Integrity Policy (“AIP”) against Ranbaxy Laboratories Limited’s (“Ranbaxy”) Paonta Sahib manufacturing facility in India.  FDA takes such regulatory action under the Agency’s AIP procedures when FDA believes that a company’s actions raise significant questions about the integrity of data in marketing applications. 

According to FDA’s AIP letter to Ranbaxy, the Agency “has determined that [Ranbaxy] submitted untrue statements of material fact in abbreviated and new drug applications filed with the Agency.  These findings concern the submission of information, such as from stability test results in support of pending and approved drug applications, from the Ranbaxy Laboratories Limited site located at Paonta Sahib, Sirmour District, Himachal Pradesh, India . . . .”  FDA’s AIP letter asks Ranbaxy to cooperate with the Agency to resolve the questions of data integrity and reliability, which would include implementing a Corrective Action Operating Plan to provide assurance of the integrity and reliability of data from the Paonta Sahib facility.  Importantly, FDA notes in the AIP letter that:

In accordance with FDA policy, the Agency will assess the validity of the data and information in all of Ranbaxy's affected applications which contain data developed at the Paonta Sahib site. . . .  This means that the Agency does not intend ordinarily to conduct or to continue its normal substantive scientific review (including review of data and labeling) of any such pending application or supplement, or of any new application or supplemental applications filed after the date of this letter, that contain data developed at the Paonta Sahib site, during a validity assessment of that application.

FDA’s latest enforcement action against Ranbaxy follows the Agency’s September 2008 issuance of two Warning Letters and an import alert concerning drug products manufactured at several Ranbaxy manufacturing facilities, including Paonta Sahib.  In addition, as we previously reported, Ranbaxy has been under investigation by FDA and the Department of Justice, and has been scrutinized by Congress.  It has been reported that Ranbaxy’s troubles with FDA were one factor that led to the introduction of the 2008 FDA Globalization Act (“FDAGA”), which, as we recently reported, has been reintroduced in the 111th Congress.  FDAGA includes provisions for FDA inspections of manufacturing facilities, requirements for risk management plans, detailed supply chain requirements, greater recall authority for FDA, country of origin labeling, and requirements for testing of purity and identity for drug products, among many others. 

By James P. Ellison –

We previously reported on FDA's Federal Register notice adjusting its civil penalties for inflation and noted our prior posts on the new civil penalty authority given to FDA in the FDA Amendments Act.  As we explained in our earlier post, FDA's rule was published as a direct final rule, meaning that it would be withdrawn if significant adverse comments were received.  Today, FDA published a notice stating that no significant adverse comments were received and therefore, the increased penalty amounts will become effective on March 27, 2009.  While it has been quiet on the civil penalty front since our earlier post, we still see the possibility for increased civil penalty activity in the coming months.

By Kurt R. Karst –      

In a rare move, the U.S. Court of Appeals for the Federal Circuit affirmed a district court decision extending a 30-month stay available under the Hatch-Waxman Amendments with respect to Teva Pharmaceutical USA, Inc.’s ANDA for a generic version of Eli Lilly and Co.’s (“Lilliy’s”) EVISTA (raloxifene HCL) Tablets. 

Under the FDC Act, an NDA holder or patent owner may choose to sue a generic applicant for patent infringement if the generic applicant submits an ANDA containing a Paragraph IV certification to an Orange Book-listed patent covering the NDA holder’s product.  If such patent infringement lawsuit is made within the statutory 45-day period, then the law mandates a 30-month stay of ANDA approval.  In that case, “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, there have been only a few cases of which we are aware where a court has extended the statutory 30-month stay on ANDA approval. 

In the current case, in late 2008, the U.S District Court for the Southern District of Indiana ruled that Teva had “recast its product more than eighteen months after it provided the original sample to Lilly and only eight months before trial is set to commence,” and that an extension of the 30-month stay was appropriate because Teva failed to cooperate in expediting the patent litigation.  Teva appealed the district court decision to the Federal Circuit.  In affirming the district court’s decision, the Federal Circuit ruled that the district court “acted within its discretion in this area.” 

In his dissent, Judge Prost emphasized that “[t]he thirty-month stay described in [FDC Act § 505(j)(5)(B)(iii)] may be extended for one reason and one reason only: ‘because either party to the action failed to reasonably cooperate in expediting the action,’” and that the district court “never related Teva’s conduct to the statutory standard.”  Judge Prost also warns of the potential consequences of the majority’s decision:

The consequences of the majority opinion are of particular importance here.  Rarely have district courts had the opportunity to address the circumstances under which the thirty-month stay may be extended or shortened.  Those courts that have addressed the issue have recognized the statutory standard and strictly abided by it in determining whether to modify the stay . . . .  To affirm in this case is to effectively eliminate the statutorily required finding, and to prematurely terminate the development of appropriate standards governing modification under [FDC Act § 505(j)(5)(B)(iii)].    

By Kurt R. Karst –      

We previously reported on a citizen petition submitted to FDA requesting that the Agency address whether the 30-month stay provisions of the Hatch-Waxman Amendments apply to a pending ANDA for a generic version of DORYX (doxycycline hyclate) Delayed-Release Tablets, an old antibiotic drug, which ANDA contains a Paragraph IV certification to a patent listed in the Orange Book in accordance with § 4(b)(1) of the recently-enacted QI Program Supplemental Funding Act of 2008 (the “QI Act”).  (The "QI" stands for Qualifying Individual.) 

The petition argues that the plain language of the QI Act requires application of the 30-month stay provisions of the original Hatch-Waxman Amendments, rather than the version of the statute amended by the Medicare Modernization Act (“MMA”), which limits 30-month stays such that a generic applicant with a pending ANDA that amends its application to add a Paragraph IV certification to a later-listed patent is not subject to a 30-month stay in connection with that certification.  In support of this position, the petition cites QI Act § 4(a) (to be codified at FDC Act § 505(v)(4)), which states:

Notwithstanding section 125, or any other provision, of the Food and Drug Administration Modernization Act of 1997, or any other provision of law, and subject to the limitations in [new FDC Act §§ 505(v)(1)-(3)], the provisions of the Drug Price Competition and Patent Term Restoration Act of 1984 shall apply to any drug subject to [new FDC Act § 505(v)(1)] or any drug with respect to which an election is made under [new FDC Act § 505(v)(2)(A)]. [(emphasis added)]

A similar citizen petition was recently submitted to FDA on behalf of Medicis Pharmaceutical Corporation (“Medicis”) concerning SOLODYN (minocycline HCl) Extended Release Tablets, another old antibiotic drug.  According to FDA’s Paragraph IV Certification List, ANDAs containing a Paragraph IV certification to a QI Act Orange Book-listed patent have been submitted to FDA with respect to DORYX and SOLODYN, as well as to a third drug, EVOCLIN (clindamycin phosphate) Foam, 1%.  The Orange Book patent listings and Paragraph IV certifications for these three products were made in accordance with the transition provisions in § 4(b) of the QI Act and FDA’s November 2008 draft guidance document, which describes the Agency’s current thinking on the implementation of § 4(b)(1).  QI Act § 4(b) includes three transition provisions on Orange Book patent listing, certification, and 180-day exclusivity for each ANDA applicant that not later than 120 dates after enactment of the QI Act (i.e., February 5, 2009) amends a pending application to contain a Paragraph IV certification to a newly listed old antibiotic drug patent.  FDA has already approved one ANDA for a generic version of SOLODYN that qualifies for 180-day exclusivity; however, FDA did not have to resolve the 30-month stay issue because the applicant was not sued for patent infringement within the statutory 45-day period.  (In fact, the generic applicant entered into a settlement and license agreement with Medicis under which Medicis agreed not to sue for patent infringement within the statutory 45-day period.)

In addition to arguing that the original Hatch-Waxman Amendments apply, such that a 30-month stay is available if a generic applicant with an ANDA pending before October 8, 2008 (when the QI Act was enacted) amends that application to include a Paragraph IV certification to a patent listed in the Orange Book pursuant to the QI Act’s transition provisions, the Medicis petition argues that even if the MMA’s 30-month stay rules apply, then Medicis is entitled to a 30-month stay.  First, Medicis argues that ANDAs amended to contain a Paragraph IV certification pursuant to the QI Act should be treated as having been submitted after the patent information was filed.  According to Medicis, under this interpretation, the QI Act “recalculates the submission date of a covered ANDA to the first day on which the first possible application containing a Paragraph IV certification could have been submitted” so that a 30-month stay is available.  Second, Medicis argues that patents covering old antibiotics listed in the Orange Book in accordance with that transition provision at QI Act § 4(b)(1) should be treated as having been filed in the original ANDA, instead of in an amendment, thus providing for 30-month stay availability.  Medicis contends that this interpretation “strikes a fair balance . . . between innovator and generic interests by providing innovators with the opportunity for adjudication of patent infringement claims before approval of an ANDA, while achieving the MMA’s purpose of preventing multiple 30-month stays against the same ANDA.”   

It is unclear how soon FDA will respond to the two petitions or will otherwise take action on pending ANDAs affected by the petitions.  Under FDC Act § 505(q), FDA is required to respond within 180-days after receiving the petitions; however, a petition that does not raise public health issues is not supposed to delay generic drug approval.  Therefore, it is possible that if FDA internally decides that it will not grant the two petitions, the Agency could make approval decisions and later respond to the petitions.  Indeed, this is the path FDA took in early 2008, when the Agency approved ANDAs for generic CAMPTOSAR (irinotecan HCl) notwithstanding a pending citizen petition that FDA ultimately denied in July 2008.
  

By Ricardo Carvajal—

During a session at the Food and Drug Law Institute’s Second Annual Conference on Nanotechnology Law, Regulation, and Policy, senior FDA staff confirmed that the agency does not intend to issue regulations specific to products derived through nanotechnology, or to establish a definition of nanotechnology for regulatory purposes. Furthermore, the agency continues to regard the 2007 Nanotechnology Task Force Report as current, and has no plans to update it.

Representatives from the different FDA centers addressed their plans to develop and issue guidance documents that address nanotechnology. CFSAN has already updated its guidance on the kinds of information that the agency requires in regulatory submissions for food contact substances, and has a similar update for direct additive submissions nearing publication. CFSAN is also considering a guidance on the regulatory consequences of changes in the manufacture of a substance covered by a food additive regulation or a new dietary ingredient notification. With respect to color additives, CFSAN has a guidance in the early stages of development.

Neither CDER nor CDRH intend to issue nanotechnology-specific guidance documents in the near term. Both centers expressed a preference for developing additional experience with the issues posed by products derived through nanotechnology before trying to address them through guidance. In the interim, developers and manufacturers of all FDA-regulated products derived through nanotechnology are encouraged to consult with FDA early on to ensure that concerns about safety, efficacy, and quality are adequately addressed.