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.

By Ricardo Carvajal

The Second Circuit Court of Appeals has rejected  the New York State Restaurant Association’s (NYSRA’s) challenge to a New York City Board of Health (NYC) regulation requiring all menu boards and menus in chain restaurants with 15 or more establishments nationally to bear calorie content information for each menu item. The appellate court held that NYC’s regulation is neither expressly preempted by the Nutrition Labeling and Education Act of 1990 (NLEA), nor does it violate the First Amendment.

In concluding that the NLEA does not expressly preempt NYC’s regulation, the court relied in part on FDA’s amicus curiae brief, to which the court granted deference under Skidmore v Swift & Co., 323 U.S. 134 (1944).  In disposing of NYSRA’s First Amendment challenge, the court found support for NYC’s regulation in a report commissioned by FDA that discusses the public health challenges posed by obesity, the apparent link between obesity and dining out, and the potential benefits of providing diners with calorie information.

By John A. Gilbert and Larry K. Houck –

The Drug Enforcement Administration (“DEA”) has published a notice of proposed rulemaking to control Tapentadol as a schedule II substance under the Controlled Substances Act.  Schedules of Controlled Substances: Placement of Tapentadol Into Schedule II, 74 Fed. Reg. 7,386  (Feb. 17, 2009).  The Food and Drug Administration (“FDA”) approved Tapentadol, a new molecular entity, for marketing as a prescription drug for moderate-to-severe acute pain on November 20, 2008.  The Assistant Secretary for Health of the Department of Health and Human Services sent a scientific and medical evaluation of the drug to DEA, with the recommendation that it be placed in schedule II.  DEA found that Tapentadol has a high potential for abuse, has accepted medical use in treatment in the U.S. and its abuse may lead to severe psychological or physical dependence.

 Tapentadol is a centrally-acting synthetic analgesic that activates opioid receptors in the brain, spinal cord and gastrointestinal tract, and also inhibits reuptake of norepinephrine.  See FDA News, FDA Approves New Drug to Alleviate Moderate to Severe Pain, Nov. 24, 2008.  Although Tapentadol is a new molecular entity with no reports of diversion, abuse or law enforcement encounters, it “shares substantial pharmacological effects and abuse potential with other schedule II opioid analgesics, e.g., morphine, oxycodone, and hydromorphone.”  74 Fed. Reg. 7,386.

 Control of Tapentadol will subject handlers to registration and inventory requirements.  Tapentadol’s placement into schedule II will require compliance with specific schedule II security, quota, recordkeeping, ARCOS reporting and order form requirements.  

 Tapentadol is manufactured by Janssen Ortho, LLC, in doses of 50, 75 and 100 mg oral tablets.

 DEA requires that written comments on the proposed scheduling be postmarked on or before March 19, 2009, and that electronic comments be sent on or before midnight, EST, on March 19, 2009.

By Kurt R. Karst –      

2008 was a banner year for orphan drug designations.  FDA’s Office of Orphan Products Development (“OOPD”), which, since September 2007, has been under the leadership of Timothy Coté, M.D., M.P.H., designated a record 165 products for orphan (i.e., rare)  diseases and conditions.  FDA also approved 15 orphan products in 2008.  The 2008 orphan drug designation figure continues a recent trend in an uptick in designations.  From 2004 to 2007, OOPD granted 130, 122, 141, and 119 designations, respectively.  From 1983 to 2003, the greatest number of orphan drug designations in a single year was 95.  The table below illustrates OOPD’s designation and FDA’s orphan drug approval track record since the enactment of the Orphan Drug Act of 1983 (“ODA”).

It is unclear whether the recent increase in orphan drug designations reflects a shift in OOPD policy, or whether the Office is receiving more designation requests.  Our experience is that the depth and thoroughness of OOPD review has certainly not decreased.  In fact, OOPD seems to be placing a greater emphasis on the scientific rationale and medical plausibility components of an orphan drug designation request than it has in the past.  Thus, we believe the increase in orphan drug designations is largely a function of the quantity of requests OOPD is receiving.    

Orphan drug designation qualifies a company for several benefits under the ODA, as amended.  These benefits include a 7-year period of orphan drug exclusivity upon product approval (which generally prevents FDA from approving another firm’s version of the “same drug” for the same disease or condition for 7 years), a tax credit for certain clinical testing expenses for the orphan drug, written guidance on the non-clinical and clinical studies needed to obtain marketing approval of an orphan drug, and orphan drug grants.  In addition, there are certain user fee, pediatric assessment (i.e., FDC Act § 505B(k)), and “extra-statutory” benefits for orphan drugs (e.g., the quantity and quality of evidence needed to support the approval of an orphan product seems to reflect the understanding that there is a limited subject population in which to study the product – see ICH/FDA, Guideline for Industry: The Extent of Population Exposure to Assess Clinical Safety: For Drugs Intended for Long-term Treatment of Non-Life-Threatening Conditions, at 4 (Mar. 1995)).  

By John A. Gilbert & Larry K. Houck –      

WMSN-TV Fox 47 of Madison, Wisconsin, recently reported that pharmacies are experiencing difficulty obtaining oxycodone to fill their patients prescriptions.  Oxycodone, a schedule II opioid painkiller, is indicated for patients suffering from moderate to severe pain.  The report stated that “[a] DEA spokesperson in Chicago says this is not a nationwide shortage, and if pharmacies can’t get supply, it’s likely their manufacturer has reached its quota.”

While there may not be a nationwide oxycodone shortage, pharmacies and hospitals outside Wisconsin have also been unable to obtain the drug.  Oxycodone has been reported in short supply in Oregon and Washington, as well as in parts of California, Colorado and Maine.

The shortages have been attributed to several factors.  Some have blamed DEA for delaying the annual quota, giving manufacturers a late start.  Others have said that manufacturers have already hit their quota and were forced to cease production.  A recall by manufacturer Mallinckrodt and cutbacks by Ethex have also purportedly contributed to the problem.  One pharmacy expert observed that a few years ago five companies manufactured extended-release oxycodone and that four of the companies no longer manufacture the drug.

Other than the statement by the DEA spokesperson in Chicago, there has been no mention of the shortage by the agency.  The Controlled Substances Act (“CSA”) requires DEA to establish quotas that control the quantity of schedule I and II controlled substances that may be manufactured in the United States in a calendar year.  21 U.S.C. § 826.  DEA establishes an annual aggregate quota for each schedule I or II substance.  21 U.S.C. § 826(a).  The agency assigns individual manufacturing quotas to manufacturers of controlled substances such as oxycodone in bulk.  21 U.S.C. § 826(b).  DEA issues procurement quotas that authorize manufacturers to procure a basic class of schedule I or II substances to make dosage forms.  Manufacturers can only manufacture quantities within their assigned manufacturing quota and they may only procure source materials or manufacture dosage forms within their procurement quota.  Manufacturers apply for quotas in April of the year prior to the year of the quota request.

DEA regulations require the agency to publish aggregate production quotas on or before May 1 of each year, and individual procurement quotas and individual manufacturing quotas on or before July 1, 21 C.F.R. §§ 1303.11(c), 1303.12(c), 1303.21(a).  The CSA requires DEA to establish individual manufacturing quantities on or before October 1.  21 U.S.C. § 826(c).  DEA published the proposed aggregate production quotas for 2009 on November 7, 2008 and “established initial aggregate production quotas” for 2009 on December 29, 2008.

By J.P. Ellison –

Twenty-Seven Attorneys General have given FDA prior approval authority over Bayer’s Direct-to-Consumer (“DTC”) television and print advertising for its prescription oral contraceptive Yaz, and also required to company to run a $20 million corrective advertising campaign as part of a settlement agreements with the states (see press releases here and here).

The AGs were able to achieve this result even though the FDC Act is clear that the enforcement of the FDC Act can only be brought in the name of the FDA (the provision in FDC Act § 310 which allows States to bring actions relating to food did not apply here).  Though FDA “collaborated” with the state AGs and thus was a seemingly willing third party beneficiary of the settlement agreements, it was not a party to the litigation.

This is somewhat curious because, while the AG’s apparent leverage for the 2009 settlements came from earlier 2007 settlements with Bayer concerning its drug Baycol (see here and here), the AG press releases plainly state that the impetus for their actions was  an October 2008 FDA Warning Letter to Bayer concerning two Yaz TV spots.

The FDA Warning Letter alleges violations of the FDC Act, which one would think the FDA would enforce through agency action.  It’s equally clear that FDA’s position is that Warning Letters, like the one that Bayer received, are not final agency action.  FDA’s Regulatory Procedures Manual states that “[a]Warning Letter is informal and advisory . . . . [T]he agency does not consider Warning Letters to be final agency action on which FDA can be sued.”  So while FDA never took final agency action, the states did, and FDA has prior approval authority as a result.

While this settlement was announced shortly after President Obama took office and could be seen as a rollback on the Bush era FDA preemption doctrine, it seems likely that this settlement was agreed to in principle prior to the Administration change.  Thus, given the expectations for this administration, one can only expect increased state AG and FDA collaboration in the coming months.

By Bill T. Koustas –

On February 9, 2009, FDA (or “the Agency”) announced it has invited the sponsors of opioid drug products to a private meeting in March in order to begin the process of developing Risk Evaluation and Mitigation Strategies (“REMS”) that will impact 24 opioid products from 16 different sponsors.  This will be the first class-wide REMS program instituted by FDA.  While sponsors of investigational opioids are not immediately affected, the meeting outcome and eventual REMS will undoubtedly affect their products as well.      

According to FDA, the risks that the REMS is intended to mitigate are: (1) the use of certain opioid products in patients who are not opioid tolerant; (2) abuse; and (3) accidental and intentional overdose.  The Food and Drug Administration Amendments Act of 2007 (“FDAAA”) gives FDA the authority to require REMS for approved products when it becomes aware of new safety information and determines that a REMS is necessary to “ensure the benefits of the drug outweigh the risks of the drug,” but has no express provisions authorizing class-wide REMS. FDC Act § 355-1(2).  The Agency, however, has broad discretion in determining what constitutes “new safety information” and would likely defeat a challenge that it failed to make the requisite finding for each individual drug.  While FDA’s public statement regarding this issue notes that the Agency “recognizes the need to achieve balance between appropriate access and risk mitigation,” it is unclear what REMS elements will be required for this class of products.  In a call with the media, Dr. John Jenkins, Director of the Office of New Drugs, indicated that the REMS may include added labeling and patient monitoring among other elements to assure safe use.

According to FDA’s announcement, the opioid drugs affected by this announcement include both brand name and generic products that contain fentanyl, hydromorphone, methadone, morphine, oxycodone and oxymorphone.  The meeting described in the letter signed by Dr. Bob Rappaport, Director of the Division of Anesthesia, Analgesia and Rheumatology Products, is scheduled to take place on March 3, 2009 at 3:30pm on FDA’s White Oak campus.  Implicitly acknowledging that developing class-wide REMS for these drug products is complicated and potentially controversial, the Agency noted in the announcement that it is also planning to hold several meetings with other federal agencies, non-government organizations, patient and consumer advocates, pain and addiction treatment advocates and other health care professionals and stakeholders.  Additionally, the Agency is planning a public meeting on this issue in late spring or early summer to permit more public participation.  FDA expects to inform the sponsors of the affected opioid products regarding the required REMS after the public meeting. 

FDA will likely consult with the Drug Enforcement Administration ("DEA") on the class-wide REMS.  The Controlled Substances Act and DEA regulations require that manufacturers and registrants of controlled substances maintain effective controls against diversion and compliance with REMS could arguably be viewed as a part of this duty.  Manufacturers will need to consider that DEA will evaluate compliance with REMS as a factor in determining ongoing compliance with DEA requirements.

By Ricardo Carvajal –      

Disagreeing with an earlier New Jersey district court decision, a California district court has ruled that there is no federal preemption of an unfair competition claim against the manufacturer of a food that contains high fructose corn syrup ("HFCS") and is labeled as “all natural.”  According to the decision, the claim is not expressly preempted by FDC Act section 403A, nor is the claim impliedly preempted under the doctrines of field or conflict preemption.  On the question of implied preemption, the California court rejects as unpersuasive the reasoning relied on by a New Jersey district court to reach the opposite conclusion (Holk v. Snapple Beverage Corp., 574 F.Supp.2d 447 (D.N.J. 2008)).  This latest decision is likely to add to the existing confusion over the precise contours and reach of the doctrine of implied preemption in food liability cases.  Notably, FDA has indicated that products that contain HFCS can be labeled as "natural," depending on how the HFCS is made.