FDA Law Blog

KV Says “Heckler/Chaney Defense” is Inapplicable in Appeal Concerning Compounded 17P and Orphan Drug MAKENA

By Kurt R. Karst –      

Briefing is underway in K-V Pharmaceutical Company’s (“KV’s”) appeal of a September 2012 decision from the U.S. District Court for the District of Columbia that stymied the company’s efforts to “restore” orphan drug exclusivity for the pre-term birth drug MAKENA (hydroxyprogesterone caproate) Injection, 250 mg/mL, the compounded version of which is known as “17P.”  In its Opening Brief, KV presses its case that FDA’s decision not to take enforcement action against 17P compounders and the Agency’s issuance of a March 30, 2011 press release to that effect (referred to KV in its brief as “FDA’s Statement”) is the equivalent of an order or license reviewable in court, and that FDA caved to political pressure when it decided not to take enforcement action against 17P compounders.   

As we previously reported (here and here), KV filed a Complaint and a Motion for Temporary Restraining Order and Preliminary Injunction alleging that FDA and the Department of Health and Human Services violated myriad provisions of the FDC Act, the Administrative Procedure Act (“APA”) § 706(2), and the Due Process Clause of the Fifth Amendment to the U.S. Constitution by failing to take sufficient enforcement action to stop the unlawful competition with MAKENA by pharmacies that compound 17P.  FDA filed a Motion to Dismiss arguing, among other things, that KV’s claims are not justiciable for lack of standing, and that even if KV can establish standing, certain Agency statements concerning compounded 17P are not subject to judicial review under the APA because FDA’s decisions not to take enforcement action are committed to the agency’s discretion under Heckler v. Chaney, 470 U.S. 821 (1985).  In Chaney, the U.S. Supreme Court held that “an agency’s decision not to prosecute or enforce, whether through civil or criminal process, is a decision generally committed to an agency’s absolute discretion,” and as such, is presumed to be unreviewable under the APA. 

After finding that KV alleged sufficient facts to support standing, the D.C. District Court found KV’s first three Counts concerning orphan drugs (FDC Act § 527(a)), compounding (FDC Act § 503), and new drug approval (FDC Act §§ 505(a) and 301(d)) unreviewable, because APA § 701 “precludes judicial review of final agency action, including refusals to act, when review is precluded by statute or ‘committed to agency discretion by law,” and because Chaney is controlling.  Addressing Count IV of KV’s Compliant alleging that FDA violated FDC Act § 801(a) by permitting foreign-manufactured active pharmaceutical ingredient to be imported into the United States for compounding into 17P, the court found that the Count failed to state a claim.

Interestingly, another D.C.  District Court decision, also on appeal to the D.C. Circuit, Beaty v. FDA, 853 F. Supp. 2d 30 (D.D.C. 2012), appeal docketed sub nom. Cook v. FDA, Nos. 12-5176, 12-5266 (D.C. Cir. May 31, 2012), came out the other way for FDA when the Agency pressed Chaney as a defense.  In that case, the court found that FDA “ignore[d] an administrative directive” when the Agency exercised enforcement discretion with regard to the importation of unapproved sodium thiopental for use by state Departments of Corrections to carry out death sentences by lethal injection.  (See our previous post here.)

KV argues in its Opening Brief that the case falls outside of the Chaney framework for three reasons:

First, FDA’s Statement involves active solicitation of unlawful conduct, not mere non-enforcement.  Second, FDA’s Statement announces a policy applicable to more than 1,000 compounders, not a single-shot decision not to proceed in a particular case involving a particular party or parties.  Third, FDA’s action in making a public statement intended to elicit unlawful conduct that otherwise would not have occurred is an abdication of FDA’s responsibility to administer the FDCA.

Moreover, says KV, even if Chaney applies, “its rebuttable presumption of unreviewability is rebutted here” because the factors identified in the Supreme Court’s decision as supporting enforcement discretion, such as enforcement priorities and quality of evidence, are absent.  “FDA’s Statement does not invoke any of the factors to which enforcement discretion applies.”

FDA Presses “Heckler Defense” in Appeal of Unapproved Thiopental Sodium Death Row Inmate Case

By Kurt R. Karst –      

FDA’s opening brief in the Agency’s appeal of a March 27, 2012 Memorandum Opinion and accompanying Order issued by Judge Richard J. Leon of the U.S. District Court for the District of Columbia (as modified by a June 22, 2012 Order) in Beaty v. FDA, 853 F. Supp. 2d 30 (D.D.C. 2012) (now Cook v. FDA) concerning FDA’s exercise of enforcement discretion with regard to the importation of unapproved sodium thiopental for use by state Departments of Corrections to carry out death sentences by lethal injection is all about the U.S. Supreme Court’s decision in Heckler v. Chaney, 470 U.S. 821 (1985).  In Heckler, the Court rejected a challenge to FDA’s determination that the Agency would not take enforcement action in the lethal injection context, and held that FDA’s determinations about the circumstances in which the Agency would take enforcement action were not subject to judicial review, because “agency refusals to institute investigative or enforcement proceedings are committed to agency discretion.”  In Beaty, the outcome was different.  

As we previously reported (here and here), Judge Leon’s decision to grant summary judgment to Plaintiffs stems from a February 2011 lawsuit (amended in July 2011) brought against FDA by death row inmates alleging violations of the Administrative Procedure Act (“APA”) and the FDC Act.  Specifically, the Plaintiffs alleged that FDA violated the APA (5 U.S.C. § 706(2)(A)) by improperly allowing shipments of a misbranded and unapproved new drug to enter the U.S. contrary to the FDC Act, and violated the APA (5 U.S.C. § 706(2)(A)) by departing from longstanding Agency policies and undermining the purpose of the FDC Act. 

At issue in the case is FDC Act § 801(a), which concerns imports.  The statute states, in relevant part, that “[i]f it appears from the examination of such [imported] samples or otherwise” that the product violates the FDC Act’s misbranding or new drug approval requirements, “then such article shall be refused admission” (emphasis added).   Although FDA contended that FDC Act § 801(a)does not impose a mandatory duty on the Agency to refuse admission of an import, Judge Leon, in a rather colorful decision, ruled that the statute is clear: “Congress’ intent was for ‘shall’ to impose a mandatory obligation on [FDA] to refuse to admit the misbranded and unapproved drug, thiopental, into the United States.”  Judge Leon also ruled that FDA’s determination not to pursue enforcement action was arbitrary and capricious.  As a result, Judge Leon permanently enjoined FDA “from permitting the entry of, or releaseing any future shipments of, foreign manufacted thiopental that appears to be misbranded or in violation of (FDC Act § 505].” 

FDA had argued that U.S. Supreme Court’s Heckler decision should apply to the case at bar.  In issuing his decisions, however, Judge Leon distinguished Heckler, and wrote that “[u]nlike in Heckler, here, the FDA’s decision did not involve a decision whether to initiate enforcement proceedings against a violator of the Act; rather, it involved a decision to ignore an administrative directive.”  The bottom line, wrote Judge Leon, is that “FDA appears to be simply wrapping itself in the flag of law enforcement discretion to justify its authority and masquerade an otherwise seemingly callous indifference to the health consequences of those imminently facing the executioner’s needle.  How utterly disappointing!”

FDA, in the Agency’s opening brief, attempts to hammer home for the DC Circuit why Heckler applies and is in controlling in this case: 

The district court’s contrary conclusion was premised almost entirely on the use of the word “shall” in a sentence providing that “[i]f it appears” that an FDA-regulated article fails to comply with certain requirements, “then such article shall be refused admission.”  21 U.S.C. § 381(a).  The presumption in favor of enforcement discretion is not overcome by the bare use of words like “shall,” which are routinely interpreted to preserve rather than eliminate administrative discretion in the enforcement context.  Here, the sentence upon which the district court relied merely describes the consequences of a determination by FDA, after any appropriate administrative procedures, that enforcement action is warranted and a given article is subject to removal.  It in no way constrains the agency’s discretion over whether to make such a determination in the first place.

As the Supreme Court recognized in Heckler, overriding an agency’s discretion to decide whether to engage in enforcement proceedings interferes with the agency’s determinations about whether particular enforcement actions are counterproductive or unduly tax agency resources in relation to other responsibilities that the agency may regard as more pressing.  FDA exercises enforcement discretion to not impede controlled imports of medically necessary drugs in response to drug shortages in the United States, and to avoid diverting agency resources on individual attempts to import small amounts of foreign prescription drugs for personal use.  The district court’s reasoning provides no basis for curtailing these exercises of the agency’s discretion in favor of an inflexible mandate to undertake enforcement proceedings in response to every apparent violation of the statute that occurs in the import context, and its judgment should be reversed. 

Interestingly, in another recent case also concerning FDA’s exercise of enforcement discretion, but in the context of compounded versions of hydroxyprogesterone caproate injection that compete with the approved drug MAKENA marketed by K-V Pharmaceutical Company, Judge Amy Berman Jackson of the DC District Court ruled for FDA.  In that case, which is not cited in FDA’s opening brief, Judge Jackson found the Plaintiff’s claims unreviewable, because the APA “precludes judicial review of final agency action, including refusals to act, when review is precluded by statute or ‘committed to agency discretion by law,’” and because Heckler is controlling (see our previous post here).  Last week, K-V appealed that decision to the DC Circuit (Docket No. 12-5349). 

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House Passes FDA Reform Act of 2012; Next Up – Conference Committee

By Kurt R. Karst –      

After a round of congratulatory speeches, the U.S. House of Representatives passed H.R. 5651, the FDA Reform Act of 2012, as amended, on May 30th by a vote of 387-5.  Unlike the U.S. Senate, which passed its version of the bill last week (see our previous post here), the House did not have to slog through a slew of amendments before passing its bill.  The House bill was passed in relatively short order at 7:00 PM.  Accompanying H.R. 5651 is a House Report deatailing the bill’s history and including a section-by-section analysis.  Both bills reauthorize and amend old (PDUFA and MDUFA) and establish new (GDUFA and BsUFA) user fee statutes, permanently reauthorize the Best Pharmaceuticals for Children Act and the Pediatric Research Equity Act, and create several new provisions of law, among other things.  (The draft performance goals and procedures for each of the user fee pacts are available here, here, here, and here.)

Now that the House and Senate have passed H.R. 5651 and S. 3187 (the FDA Safety and Innovation Act), respectively, focus will move to a conference committee, which will iron out differences between the bills and reach a compromise.  There are many differences between the Senate and House bills – some major and some minor – although the user fee provisions in both bills are almost identical.  The Senate bill includes provisions on drug track and trace, Risk Evaluation and Mitigation Strategies, and changes to the Controlled Substances Act not included in the House bill.  Meanwhile, the House bill includes provisions on generic drug 180-day exclusivity forfeiture, citizen petitions, and drug shortages not included in the Senate bill.  The Congressional Research Service has put together a handy-dandy side-by-side comparison of current law, S. 3187 (as passed), and H.R. 5651 (suspension document).  The expectation among House and Senate leaders is to have a compromise bill voted on and on the President’s desk by the end of June or early July. 

Meanwhile, on May 31st the House Ways and Means Committee is scheduled to mark up H.R. 436, the Protect Medical Innovation Act of 2011.  The bill would amend the Internal Revenue Code of 1986 to repeal the 2.3% medical device excise tax created by the Affordable Care Act that is schedule to take effect in 2013.  According to a report prepared by the Joint Committee on Taxation, the medical device excise tax repeal is in need of a $29 billion offset.  The excise tax has stirred considerable controversy (see here and here) and has played a factor in election year politics, according to Politico. (UPDATE: The Ways and Means Committee voted 23-11 in favor of the repeal - see here.)

REMINDER:  HP&M is hosting a webinar, Garbage Runs, Fake Identities, and Surprise Home Visits; Strategies to Deal With FDA's Nontraditional Investigative Tools, on Wednesday, June 20, 2012 from 12:30 - 2:00 p.m. ET.  Click here to register.

U.S. Senate Slogs Through Amendments and Passes FDA Safety and Innovation Act; Onward to the House Bill

By Kurt R. Karst –      

After days of debate and a slew of proposed amendments, the U.S. Senate passed S. 3187, the FDA Safety and Innovation Act, on Thursday afternoon by a roll call vote of 96-1.  Senator Bernie Sanders (I-VT), who cast the lone vote against passage, issued a statement explaining his vote.  A similar process may unfold in the U.S. House of Representatives as that chamber considers its version of a legislative package, H.R.5651, the Food and Drug Administration Reform Act of 2012.  H.R. 5651 is ready for a floor vote, and House Republicans have indicated that they want to get a final bill to the President by July 4th.  Late on May 24th, the Congressional Budget Office released a cost estimate of H.R. 5651.  Both the Senate and House bills reauthorize old (PDUFA and MDUFA) and establish new (GDUFA and BsUFA) user fee statutes, and create several new provisions of law.

Over the past week, somewhere in the neighborhood of 40 amendments to S. 3187 were introduced in the Senate – see here, here, here, and here for the text of those amendments.  That number was winnowed down to less than 20 amendments, which the Senate debated and voted on on Thursday, including votes on a couple of high-profile issues (e.g., reimportation and patent settlement agreements).  Among other things, the Senate did not consider items such as an amendment from Sen. Orrin Hatch (R-UT) to repeal the medical device excise tax and generic drug labeling and preemption legislation.  (The National Association of Attorneys General recently sent a letter to members of the Senate Judiciary Committee expressing support for the Patient Safety and Generic Labeling Improvement Act.)

Below is an overview of how the chips fell for each amendment considered and a brief summary of each amendment (except Senate Amendment No. 2122, a substitute version of  S. 3187, which was agreed to by unanimous consent, and the text of which is available here).  

Amendments Agreed To By Unanimous Consent Or Voice Vote

Amendment No. 2125 (Sen. Cardin) – Ensuring Adequate Information Regarding Pharmaceuticals For All Populations, Particularly Underrepresented Subpopulations, Including Racial Subgroups:  The amendment would require FDA to “review and modify, as necessary, the [FDA’s] communication plan to inform and educate health care providers, patients, and payors on the benefits and risks of medical products, with particular focus on underrepresented subpopulations, including racial subgroups.”

Amendment No. 2141 (Sen. Cardin) – Report On Small Business:  FDA is required to submit a report to Congress (not later than one year after the date of enactment) that includes: “(1) a listing of and staffing levels of all small business offices at [FDA], including the small business liaison program; (2) the status of partnership efforts between [FDA] and the Small Business Administration; (3) a summary of outreach efforts to small businesses and small business associations, including availability of toll-free telephone help lines;  (4) with respect to the program under the Orphan Drug Act (Public Law 97-414), the number of applications made by small businesses and number of applications approved for research grants, the amount of tax credits issued for clinical research, and the number of companies receiving protocol assistance for the development of drugs for rare diseases and disorders; (5) with respect to waivers and reductions for small business under [PDUFA], the number of small businesses applying for and receiving waivers and reductions from drug user fees . . . ; (6) the number of small businesses submitting applications and receiving approval for unsolicited grant applications from [FDA]; (7) the number of small businesses submitting applications and receiving approval for solicited grant applications from [FDA]; (8) barriers small businesses encounter in the drug and medical device approval process; and (9) recommendations for changes in the user fee structure to help alleviate generic drug shortages.”

Amendment No. 2121 (Sen. Grassley) – Protections For The Commissioned Corps Of The Public Health Service:  This amendment offers whistleblower protections and prohibits retaliatory personnel actions.

Amendment No. 2129 (Sen. Grassley) – Regulations On Clinical Trial Registration; GAO Study Of Clinical Trial Registration And reporting Requirements:  The amendment requires the issuance of a proposed rule on the registration of “applicable clinical trials” by “responsible parties” under PHS Act § 402(j) (as amended by § 801 of the FDA Amendments Act of 2007) not later than 180 days after the date of enactment, and the promulgation of a final rule not later than 180 days after the issuance of the proposed rule.  Not later than two years after the issuance of the final rule, the Government Accountability Office (“GAO”) would be required to report on the rate of compliance and non-compliance of clinical trial registration, results reporting, and the completeness of reported data.  If problems are found, then the GAO is to make recommendations for administrative or legislative actions to increase compliance.

Amendment No. 2151 (Sen. Manchin) – Hydrocodone Scheduling:  The amendment reclassifies the scheduling of hydrocodone so that all drug products containing hydrocodone would be Schedule II controlled substances under the Controlled Substances Act.  Although hydrocodone is currently a Schedule II controlled substance, when combined with certain other drugs it is in Schedule III. 

Amendment No. 2126 (Sen. Reed) – Compliance Date For Rule Relating To Sunscreen Drug Products For OTC Human Use:  The amendment states that “[i]n accordance with the final rule issued by the Commissioner of Food and Drug entitled ‘Labeling and Effectiveness Testing; Sunscreen Drug Products for Over-the-Counter Human Use; Delay of Compliance Dates’ (77 Fed. Reg. 27591 (May 11, 2012)), a product subject to the final rule issued by the Commissioner entitled ‘Labeling and Effectiveness Testing; Sunscreen Drug Products for Over-the-Counter Human Use’ (76 Fed. Reg. 35620 (June 17, 2011)), shall comply with such rule not later than – (1) December 17, 2013, for products subject to such rule with annual sales of less than $25,000 and (2) December 17, 2012, for all other products subject to such rule.”  Senator Reed recently sent a letter to FDA expressing concern about the Agency's delay in putting sunscreen standards into effect.  The delay was also criticized by the Environmental Working Group, which is seeking certain information from FDA on the issue.

Amendment No. 2142 (Sen. Leahy) – Freedom Of Information Act (“FOIA”): The amendment concerns the receipt and protection of confidential information obtained from foreign government agencies relating to drug inspections, and states that FDA shall not be required to disclose under FOIA (or any other provision of law) “any information relating to drug inspections obtained from a foreign government agency” if certain conditions are met. 

Amendment No. 2145 (Sen. Portman) – Interstate Drug Monitoring Efficiency and Data Sharing Act of 2012:  The Attorney General would be required to “establish national interoperability standards to facilitate the exchange of prescription information across State lines by States receiving grant funds” under the Harold Rogers Prescription Drug Monitoring Program and the Controlled Substance Monitoring Program not later than one year after the date of enactment.

Amendment No. 2131 (Sen. Coburn) – Independent Assessment Of The Drug And Biologic Application Review Process:  The amendment requires FDA to “contract with a private, independent consulting firm capable of performing the technical analysis, management assessment, and program evaluation tasks required to conduct a comprehensive assessment of the process for the review of” applications under FDC Act § 505(b) and § 505(j) for drugs and PHS Act § 351(a) and § 351(k) for biologics.  “The assessment shall address the premarket review process of drugs by [FDA], using an assessment framework that draws from appropriate quality system standards, including management responsibility, documents controls and records management, and corrective and preventive action.”  Among other things, FDA would be required to “analyze the recommendations for improvement opportunities identified in the assessment, develop and implement a corrective action plan, and ensure its effectiveness.”

Amendment No. 2146 (Sen. Portman) – Synthetic Drug Abuse Prevention Act of 2012:  This amendment would make certain “cannabimimetic agents” Schedule I controlled substances under the Controlled Substances Act.

Amendments Not Agreed To

Amendment No. 2111 (Sen. Bingaman); Not agreed to by a 28-67 vote – Ensuring That Valid Generic Drugs May Enter The Market:  This amendment proposed to amend the FDC Act’s provisions with respect to “first applicant” status and 180-day marketing exclusivity for certain ANDA sponsors to address patent settlement agreements (or what opponents call “pay-for-delay” agreements). 

Amendment No. 2108 (Sen. Murkowski); Not agreed to by a 46-50 vote – Analyses Of Application For Approval Of genetically-Engineered Fish:  This amendment would have prevented FDA’s approval of any genetically modified marine or anadromous organism from taking effect until certain requirements are me. 

Amendment No. 2107 (Sen. McCain); Not agreed to by a 43-54 vote – Safe And Affordable Drugs From Canada:  The amendment would have required FDA to promulgate regulations permitting individuals to import into the United States a prescription drug (other than a controlled substance) that: “(1) is purchased from an approved Canadian pharmacy; (2) is dispensed by a pharmacist licensed to practice pharmacy and dispense prescription drugs in Canada; (3) is purchased for personal use by the individual, not for resale, in quantities that do not exceed a 90-day supply; (4) is filled using a valid prescription issued by a physician licensed to practice in the United States; and (5) has the same active ingredient or ingredients, route of administration, dosage form, and strength as a prescription drug approved by [FDA].”

Amendment No. 2109 (Sen. Sanders); Not agreed to by a 9-88 vote – Conditions On Award Of Drug Exclusivity:  The amendment proposed to terminate marketing exclusivity for drugs and biologics if the person to which such exclusivity was granted or any person to which such exclusivity is assigned commits certain violations or fails to report certain violations.
 
Withdrawn Amendments

Amendment No. 2132 (Sen. Coburn) – FDA Employee Performance Awards:  The amendment proposed to establish a system by which a portion of performance awards would be connected to the evaluation of the employee’s contribution to the goals under the various user fee agreements.  The GAO recently issued a report concerning this topic, titled “Employee Performance Standards for the Timely Review of Medical Product Applications.”

Amendment No. 2130 (Sen. Burr) – Transparency In FDA User Fee Agreement Negotiations:  The amendment would have added the following with respect to PDUFA, MDUFA, GDUFA, and BsUFA: “Notwithstanding any other provision of this section, Members of Congress or their designated staff may be present at any negotiation meeting conducted under this subsection between [FDA] and the regulated industry, if a Member of Congress decides to attend, or have his or her designated staff attend on his or her behalf.  Any staff designated under the preceding sentence may be required to comply with applicable confidentiality agreements.”

Tabled Amendments

Amendment No. 2143 (Sen. Paul); Tabled by a 78-15 vote – Dietary Supplements:  Among other things, the amendment would have prohibited the Federal government from taking “any action to prevent use of a claim describing any nutrient in a food or dietary supplement . . . as mitigating, treating, or preventing any disease, disease symptom, or health-related condition, unless a Federal court in a final order following a trial on the merits finds clear and convincing evidence based on qualified expert opinion and published peer-reviewed scientific research that – (1) the claim is false and misleading in a material respect; and (2) there is no less speech restrictive alternative to claim suppression, such as use of disclaimers or qualifications, that can render the claim non-misleading.”

Amendment No. 2127 (Sen. Durbin); Tabled by a 77-20 vote – Registration Of Facilities With Respect To Dietary Supplements:  The amendment proposed to require all dietary supplement facilities to register with FDA.  Such registration would include: (1) a description of each dietary supplement product manufactured by such facility; (2) a list of all ingredients in each such dietary supplement product; and (3) a copy of the label and labeling for each such product.  Failure to comply with registration requirements would result in misbranding of the products.  Senator Durbin's statement on the amendment is available here.

GAO Says FDA Needs to do More to Address “Economic Adulteration”

By Kurt R. Karst –      

Last week, the Government Accountability Office (“GAO”) released a report, titled “Food and Drug Administration: Better Coordination Could Enhance Efforts to Address Economic Adulteration and Protect the Public Health,” in which the GAO examines FDA’s approaches to detecting and preventing so-called “economic adulteration” of food and medical products, and the challenges FDA faces in detecting and preventing such adulteration.  The report responds to requests from Representatives Henry Waxman (D-CA), Frank Pallone (D-NJ), and John Dingell (D-MI) that the GAO review how FDA oversees the safety of products to prevent and respond to economic adulteration.  The requests followed two high-profile cases of economic adulteration involving melamine and melamine-related compounds in pet foods and oversulfated chondroitin sulfate in the blood thinner heparin – in both cases, the products were imported from China.

Economic adulteration (also known as “economically motivated adulteration”) is defined in the report to mean “the fraudulent, intentional substitution or addition of a substance in a product for the purpose of increasing the apparent value of the product or reducing the cost of its production, i.e., for economic gain.”  Economic adulteration includes, for example, “dilution of products with increased quantities of an already-present substance (e.g., increasing inactive ingredients of a drug with a resulting reduction in strength of the finished product, or watering down of juice) to the extent that such dilution poses a known or possible health risk to consumers, as well as the addition or substitution of substances in order to mask dilution.”  (The definition of “economic adulteration” used in the GAO report is the same definition FDA proposed in April 2009 as a working definition for “economically motivated adulteration” – see 74 Fed. Reg. 15,498 (Apr. 6, 2009).)  Economic adulteration, a form of “intentional adulteration” whose primary purpose is financial gain, differs from other types of adulteration – both intentional adulteration, whose primary purpose is to cause harm (e.g., bioterrorism or sabotage), and “unintentional adulteration” (e.g., adulteration for failure to follow good manufacturing practices) - says GAO in the report.  The FDC Act does not make a distinction between intentional and unintentional adulteration, but rather prohibits the introduction of adulterated food, drugs, and medical devices into interstate commerce.  Similarly, “FDA primarily approaches economic adulteration as part of its broader efforts to combat adulteration in general, such as efforts to ensure the safety of imported products.”

FDA officials and stakeholders GAO interviewed in preparing the report noted several key challenges to detecting and preventing economic adulteration, including increased globalization, an increase in supply chain complexity, and difficulties with gathering information from industry (due to concerns about sharing proprietary information).  To enhance FDA’s efforts to combat economic adulteration, GAO recommends that Commissioner Hamburg take three actions: (1) officially adopt a working definition of “economic adulteration,” because “[w]ithout such a definition, when FDA detects adulteration, it is more difficult for the agency to make a distinction between economic adulteration and other forms of adulteration to guide the agency’s thinking about how to be more proactive about this issue;” (2) “provide written guidance to agency centers and offices on the means of addressing economic adulteration;” and (3) “enhance communication and coordination of agency efforts on economic adulteration,” because “[w]ithout such communication and coordination, in these times of economic uncertainty, FDA may not be making the best use of its scarce resources.”

FDA notes in the Agency’s response to the GAO report that FDA recently established the Working Group on Economically Motivated Adulteration (“WEMA”), which is comprised of staff from all FDA centers, the Office of Regulatory Affairs, and Office of the Commissioner.  WEMA, which held its first meeting on September 23, 2011, and will use the Agency’s proposed working definition of economically motivated adulteration to identify topics of broad Agency interest, “seeks to encourage information sharing across FDA on issues relevant to economically motivated adulteration.”

Del Monte Fresh Sues FDA to Invalidate Cantaloupe Import Alert

By Ricardo Carvajal -

Del Monte Fresh Produce N.A., Inc. ("Del Monte Fresh") sued to invalidate an FDA import alert on cantaloupe from Productos Agricolas de Oriente, S.A. ("PAO"), a Guatemalan producer that is one of Del Monte Fresh’s principal suppliers.  FDA imposed the import alert as the result of a multi-state outbreak of Salmonella Panama that FDA attributed to PAO cantaloupes.  The complaint alleges that FDA’s conclusion regarding the likely source of the outbreak “was not rationally supported by the evidence available to FDA,” and that “FDA also did not take into account evidence that did not support that conclusion.”  In specific, the complaint alleges that all tests of PAO cantaloupes for Salmonella or other pathogens have been negative, that FDA inspections and other audits of PAO have been satisfactory, and that some evidence suggests that the outbreak may have been caused by cantaloupes from other sources or foods other than cantaloupe.  Thus, if the case proceeds, it will likely focus on the sufficiency of the epidemiological evidence relied on by FDA.  Given the increasing sophistication of (and reliance on) epidemiological investigations in responding to outbreaks of foodborne illness, that makes this a case to watch.

 

Will the Dog Days of Summer Offer a Reprieve to FDA and the Regulated Industry (and Your Bleary-Eyed Bloggers)? Doubtful

By Kurt R. Karst –    

Over the Independence Day holiday, in between the family BBQ and fireworks, we had a few minutes to reflect on what a hectic month June was for FDA and the regulated industry.  There were the decisions handed down by the U.S. Supreme Court in Mensing and Sorrell (here and here), and the Court’s decision to hear Caraco Pharmaceutical Laboratories, Ltd. v. Novo Nordisk A/S (Docket No. 10-844).  June also saw a host of new lawsuits and appeals, including the ReGen and PREVOR Complaints filed against FDA.  The U.S. Government Accountability Office issued a bevy of reports on issues including antibiotic resistance, the influenza pandemic, medical device recalls, and a late May report on pediatric research. 

FDA, of course, had its hands full with the AVASTIN (bevacizumab) hearing, but the Agency still found time to issue myriad guidance documents, reports, rules and regulations, and other decisions on issues including Research Use Only and Investigational Use Only products, 505(q) citizen petitions, OTC sunscreen drug products, nanotechnology, and global product safety and quality.

Things were particularly busy on Capitol Hill where a flurry of bills were introduced in June, and several missives to FDA and the regulated industry were generated (see, e.g., here, here, here, and here).  Below is a sampling of the FDA-related bills recently introduced in Congress.

• Dietary Supplement Labeling Act of 2011 (S. 1310)
• Preservation of Antibiotics for Medical Treatment Act of 2011 (S. 1211)
• Medicare Drug Savings Act of 2011 (S. 1206)
• Pandemic and All-Hazards Preparedness Reauthorization Act of 2011 (H.R. 2405)
• Safe Cosmetics Act of 2011 (H.R. 2359)
• America Rx Act of 2011 (H.R. 2296)
• Preserving Access to Life-Saving Medications Act of 2011 (H.R. 2245)
• Medical Gas Safety Act (H.R. 2227)
• Skin Cancer Prevention, Education, and Consumer Right-To-Know Act (H.R. 2132)
• Ryan Creedon Act of 2011 (H.R. 2119)

There are no signs of activity letting up for the rest of the year and into 2012.  Reauthorization of the Prescription Drug User Fee Act (“PDUFA”) – PDUFA V – will likely begin to take center stage.  The House Energy and Commerce Committee Health Subcommittee will hold a hearing on PDUFA on July 7th.  According to a hearing background memo, “[o]n September 1, 2011, FDA will publish the details of the agreement recommendations on its website.  A public meeting on the recommendations will follow in October 2011. By January 15, 2012, FDA must send its final recommendations to the Committee and the Senate HELP Committee as required by statute.”  As with previous iterations of PDUFA, PDUFA V will likely act as a vehicle to which other FDA-related measures are added, including perhaps generic drug user fees and biosimilars user fees.  As always, your intrepid bloggers will be there to report on these and other events.  

Pathway to Global Product Safety and Quality – FDA’s Report Regarding Improving the Quality of Imports

By Dara Katcher Levy –

Earlier this week, FDA announced the release of a report regarding the increasing globalization of FDA-regulated products that are consumed by Americans, and how FDA intends to improve the safety and quality of these products.  FDA states that the report was prompted by “this rapidly changing environment, and a desire to move from a posture of intercepting harmful products to anticipating and preventing the arrival of such goods.”

The bulk of the report deals with facts and figures about the increasing number of imports and how, if the numbers continue to increase at current rates, the agency, continuing as it has been, will be ill-equipped to ensure the safety and quality these products.  FDA states it plans on transforming itself over the next decade into “a truly global agency fully prepared for a regulatory environment in which product safety and quality know no borders” and will do so with an approach based on four core building blocks:

1. FDA, in close partnership with its foreign counterparts, will assemble global coalitions of regulators dedicated to building and strengthening the product safety net around the world.
2. With these coalitions, FDA intends to develop a global data information system and network in which regulators worldwide can regularly and proactively share real-time information and resources across markets.
3. FDA will continue to expand its capabilities in intelligence gathering and use, with an increased focus on risk analytics and thoroughly modernized IT capabilities.
4. FDA will effectively allocate agency resources based on risk, leveraging the combined efforts of government, industry, and public- and private-sector third parties.

Much of the report is similar to Commissioner Hamburg’s statement to the Subcommittee on Oversight and Investigations, Committee on Energy and Commerce, U.S. House of Representatives given in April of this year.   

While it is laudable that FDA is taking action, reaching out to its foreign counterparts, and issuing this report, this “rapidly changing environment” has not rapidly changed overnight and has been “rapidly changing” for some time.  It’s unclear whether this report truly represents any “new” approach, rather, it appears this is a continuation of FDA's existing approach toward imports.  Although some of the facts and figures may have been updated, the statements in the report are essentially, not new.  Similar statements have been made by the FDA for years.  President Bush established an Interagency Working Group on Import Safety back in 2007, and FDA has provided updates since on its implementation of the “Import Safety Action Plan.”  FDA’s “Enforcement Story” Chapter 9, “Operations in a Global Environment,” provided an extensive look at steps being taken back in FY 08 to ensure import safety.  These steps included "Beyond Our Borders," an initiative to establish an FDA presence in foreign countries as well as partnerships with foreign regulatory agencies that included information sharing.  Further, since 2008, FDA has launched the PREDICT (Predictive Risk-Based Evaluation for Dynamic Import Compliance Targeting) system, software utilized by FDA that tracks historical data on importers, manufacturers, products, and even countries, to determine levels of risk for proposed imports, and to create consistency in FDA's approach towards these imports from port to port. 

Commissioner Hamburg’s prepared remarks for the Center for Strategic and International Studies in February 2010, address almost the identical issues contained in the most recent FDA report, including steps FDA intends to take to address these issues.  One development that could invigorate FDA’s efforts, at least with respect to imported foods, is the recent passage of the Food Safety Modernization Act (“FSMA”).  The FSMA substantially enhances FDA’s authority over imported foods, but also imposes foreign inspection mandates that the agency has indicated are unrealistic – particularly in light of budgetary constraints.

We hope the publication of this most recent report represents additional meaningful progress in implementing FDA’s stated goals.

Letter Alleges Georgia Violated Controlled Substances Act by Importing Death Penalty Drug

By Susan J. Matthees –  

In an interesting twist in a developing story on the importation of thiopental, a drug used to administer the death penalty by lethal injection, the attorney for Georgia death row inmate Andrew Grant DeYoung sent Attorney General Eric Holder a letter alleging that the Georgia Department of Corrections (“GDC”) appears to have violated the Controlled Substances Act (“CSA”) by failing to register as an importer of thiopental and file a declaration to import the drug.  As we previously reported, six inmates on death row are suing FDA over the importation by three states of allegedly adulterated and misbranded thiopental.  Mr. DeYoung, the Georgia inmate on death row, is not one of the plaintiffs in the suit against FDA.

Thiopental (sodium pentothal) is a Schedule III nonnarcotic controlled substance.  Under the CSA, a nonnarcotic controlled substance cannot be imported unless it “is imported for medical, scientific, or other legitimate uses, and is imported pursuant to such notification, or declaration, or . . . as the Attorney General may by regulation prescribe.”  21 U.S.C. § 952(b).  The Drug Enforcement Administration (“DEA”), as delegated by the Attorney General, has promulgated regulations requiring importers of such substances to be registered and file an import declaration. 

The letter alleges that Dream Pharma Ltd., a distributor in London, England, sold and shipped thiopental to the GDC in July 2010, but that the GDC is not authorized to posses thiopental because it is not registered with DEA.  When questioned, the GDC allegedly produced a DEA-issued registration to possess Schedule III narcotics, but not Schedule III nonnarcotic substances, such as thiopental.  Further, the letter alleges that GDC failed to declare its importation of thiopental as required by 21 U.S.C. § 954(2). 

Federal law and regulations provide some exceptions to registration requirements for the Department of Defense and federal Bureau of Prisons in the case of prescribing, dispensing, or administering controlled substances, but not to procure or purchase.  21 C.F.R. § 1301.22(a).  There is also an exemption for state officials engaged in enforcing state or local laws relating to controlled substances.  Id. § 1301.24(a)(2).  It does not appear that these exemptions would apply to this situation. 

The letter asks Attorney General Holder to direct DEA and/or other appropriate agencies to investigate the GDC’s actions. 

Yet Another Import Issue Resolved by Filing a Lawsuit

By Dara Katcher Levy –

We previously blogged about the Amphastar lawsuit – a suit seeking declaratory judgment and injunctive relief with regard to FDA’s detention of two entries of semi-purified heparin.  Amphastar had responded to each of FDA's allegations,  however, the shipments remained detained. 

On November 5, Amphastar filed a Motion for Preliminary Injunction against FDA alleging that Amphastar was likely to succeed on the merits of its suit and that the company was suffering irreparable harm due to the continued detention of these shipments.  A week later, on November 12, Amphastar filed a Notice of Withdrawal without prejudice of its prior Motion for Preliminary Injunction on the basis that FDA had released the materials shortly after the November 5 Motion had been filed.

It is becoming increasingly common for import issues to be resolved through utilization of the courts (often, limited to initial pleadings) in order to compel cooperation from FDA.