By Jamie K. Wolszon –

FDA is signaling that it is considering whether to fundamentally reshape how it regulates laboratories and laboratory-developed tests ("LDTs").  LDTs, which are diagnostic tests developed and performed by a laboratory, are widely used.  For example, virtually every genetic test is an LDT.  When new diseases emerge, the initial diagnostic tests are often LDTs. 

Starting in 1992, FDA asserted that it had authority over LDTs as devices.  FDA’s position is that all LDTs are devices subject to regulation under the Federal Food, Drug, and Cosmetic Act.  The legality of FDA’s position has been disputed, but not yet been the subject of a court challenge.

FDA has adopted a policy of “enforcement discretion” over laboratories and LDTs.  However, FDA now is considering jettisoning that enforcement-discretion approach and instead adopting a new, more forceful approach to regulation for LDTs.  FDA is seeking comment on a new-risk based premarket approach at a July 19-20 public meeting.

The meeting notice is one in a series of recent signs of a more activist approach to regulating LDTs.  Less than a week before the meeting announcement, on June 10, FDA sent letters to five companies stating that their genetic diagnostic tests were unapproved, a move seen as heralding increased interest in asserting regulatory power over LDTs. 

In addition, FDA commissioner Margaret A. Hamburg and National Institutes of Health Director Francis S. Collins recently authored an article in the New England Journal of Medicine that also suggested FDA interest in a more active role in LDT oversight.  The letters, article, and meeting appear to represent a coordinated effort to extend FDA regulation over LDTs.

The July 19-20 meeting notice, published in the Federal Register on June 17, 2010, stated that for years the agency has generally exercised enforcement discretion and not enforced the regulations it claims were applicable to devices.  The notice added that the agency generally has not actively regulated LDTs. 

There have been exceptions to the hands-off approach.  Over the years, FDA has occasionally challenged a test offered by a laboratory, e.g., asserting that the test was not a true LDT.  FDA also proposed regulating as devices a single, narrowly-defined subset of LDTs, In Vitro Diagnostic Multivariate Index Assays ("IVDMIAs"), which are tests where the results of multiple markers are combined to generate an “index score.”  As previously reported, it proposed premarket review requirements for those tests in a September 7, 2006, draft guidance, and a revised draft guidance issued July 26, 2007.  It has not proposed premarket review for other subsets of LDTs.

The IVDMIA approach was widely criticized.  One of the major criticisms was that it was not risk-based.  FDA has never finalized those IVDMIA draft guidances.  According to published reports, the agency will not issue the IVDMIA guidance, but instead will focus on the more comprehensive review of LDTs.
In its meeting notice, FDA states, “[T]he agency believes it is time to reconsider its policy of enforcement discretion over LDTs.”  Expanding on its goals, FDA added, “[a]t this time, FDA believes that a risk-based application of oversight to LDTs is the appropriate approach to achieve the desired public health goals….”  After the conclusion of the public meeting and the public comment period, “FDA will move forward expeditiously to develop a draft oversight framework for public comment to provide predictability as quickly as possible.  The FDA also intends to phase in such a framework over time based on the level of risk to the test.”

Discussing the factors that brought it to the conclusion that it should abandon its years-long policy of enforcement discretion, FDA said that in the past LDTs were simple, well-characterized and understood tests for rare diseases.  Now, according to the agency, LDTs often use unregulated components, assess high-risk but common diseases, and sometimes are marketed directly to consumers.  Whether FDA’s view of LDTs is correct, will certainly be the subject of comments at the meeting.

The agenda for the meeting includes sessions on patient and clinical considerations, clinical laboratory challenges, direct-to-consumer testing, and education and outreach.  The agency has posed the following questions for the patient and clinical considerations session:

• What would patients and clinicians like to see done by the FDA with respect to LDTs?  What is ideal?  What is practical?
• How might increased FDA oversight of LDTs affect patients and clinicians?  What might be the benefits?
• What are patient expectations with regard to results obtained by an LDT?  How might increased oversight of LDTs affect these expectations?
• What is the patient’s perspective regarding tests that are non-regulated versus regulated by the FDA?
• Are physicians aware that a given diagnostic test may not have been cleared or approved by FDA?  How might this knowledge affect clinical practice?
• What are the reasons that a patient or physician might choose an LDT over an FDA cleared/approved IVD?
• What are patient’s and clinician’s expectations regarding clinical validation of LDTs?
• Examples or case studies related to LDTs.

FDA has proposed the following questions as part of the clinical laboratory challenges session:

• What are the potential benefits of increased FDA oversight of LDTs?
• What would you like to see done with respect to FDA oversight of LDTs?  What is ideal?  What is practical?
• Suggested approaches of risk stratification of LDTs
• What might be some of the specific challenges faced by clinical laboratories in meeting FDA regulations?
• How might increased oversight of LDTs affect diagnostic test innovation?
• How could increased oversight of LDTs affect diagnostics used for rare conditions?
• How might increased oversight of LDTs affect reimbursement and/or the cost of diagnostic tests for the consumer?
• What are the challenges associated with validation of LDTs for clinical laboratories?
• What will the challenges be to clinical labs with respect to diagnostic test change control under greater oversight of LDTs?
• Should the clinical and analytical validation requirements be different between FDA regulated and non-FDA regulated diagnostic tests?   

The agency has proposed the following questions for the DTC session:

• What are the major concerns associated with DTC testing?
• What is the benefit of DTC testing?  What are the risks?  What is the cost?
• Are there concerns that DTC testing could lead to consumer fraud?
• Are patients taking medical action based upon preliminary diagnostic test claims?  What are the risks and benefits? 

FDA suggests the following topics for the education and outreach session:

• What resources or educational opportunities are currently available to assist clinical laboratories in meeting FDA regulations?  What would be needed?
• What specific support will be needed by clinical laboratories from the FDA given greater LDT oversight?
• How can physicians use new genetic information? 
• Whose responsibility is it to ensure that physicians can use the information provided to them by LDTs?

Given the increasingly important role in LDTs in health care in general, and in personalized medicine in particular, the meeting is almost guaranteed to provide FDA with diverse – and strongly expressed – viewpoints.

By Wes Siegner –   

On June 14, 2010, The University of Maryland School of Law hosted the first of a series of multidisciplinary meetings being held as part of a Human Microbiome Project ELSI (Ethical, Legal, Social Implications) grant to study federal regulation of probiotics.  The team that received the grant included:

• Diane E. Hoffmann, MS, JD, Associate Dean for Academic Programs and Director, Law and Health Care Program, University of Maryland School of Law (Principal Investigator)
• Claire M. Fraser-Liggett, Ph.D, Professor of Medicine and Director, Institute for Genome Sciences,  University of Maryland School of Medicine
• Frank Palumbo, Ph.D, JD, Professor and Executive Director, University of Maryland School of Pharmacy Center on Drugs and Public Policy
• Jacques Ravel, Ph.D, Associate Professor, Institute for Genome Sciences, University of Maryland School of Medicine

Participants in the conference included members of academia and the scientific research, business, legal and federal regulatory communities.  The National Institutes of Health and the Federal Trade Commission are participating in the study, and representatives from the Food and Drug Administration attended as observers.  The agenda for the first meeting, including speakers for the first day, can be found here.

The first all-day meeting focused on achieving a broad-based understanding of the science relating to probiotics and the current federal regulatory framework into which products containing probiotics fall.  As planned, this meeting was a question-generating session.  Subsequent sessions will focus more on attempting to find consensus answers to the complex regulatory questions that surround products containing probiotics.  The next meeting is being planned for January 2011.

By Kurt R. Karst –   

With all of the FDA-related amendments being introduced for consideration to the Tax Extenders Act (H.R. 4213), including the Preserve Access to Affordable Generics Act to address patent settlement agreements and an amendment to legislatively extend a patent covering The Medicines Company’s ANGIOMAX (bivalirudin), it was a fait accompli that Sen. Bill Nelson (D-FL) would reintroduce his Drug Price Competition Act by proposing it as an amendment to the bill.  That happened on June 15th, with the submission of SA4361.

SA4361, which is viewed by some as a complement to the Preserve Access to Affordable Generics Act, appears to be identical to Sen. Nelson’s S. 1315, which was introduced last June.  Rep. Alcee Hastings (D-FL) introduced a companion bill (H.R. 3777) in the House of Representatives.  Rep. Hastings also initially proposed his bill as an amendment to the House Health Care Reform Bill last November, but then withdrew it from consideration.  In January 2010, before the election of Scott Brown (R-MA) to the Senate, the American Antitrust Institute, among several other organizations, penned a letter to Senate Majority Leader Harry Reid (D-NV) and House Speaker Nancy Pelosi (D-CA) encouraging inclusion of the Drug Price Competition Act in the final Health Care Bill, along with a per se ban on patent settlement agreement payments. 

As we previously reported (here and here), Sen. Nelson’s legislation would amend the definition of “first applicant” at FDC Act § 505(j)(5)(B)(iv)(II)(bb) with respect to 180-day exclusivity eligibility so that certain subsequent ANDA applicants could trigger and also be eligible for such exclusivity.  Specifically, under SA4361, a subsequent applicant subject to a first applicant’s 180-day exclusivity eligibility could qualify as a “first applicant,” and could obtain approval and trigger 180-day exclusivity for all first applicants if there is no timely filed patent infringement lawsuit arising from its Paragraph IV certification, or if there is a timely filed lawsuit and there is a court decision (including a district court decision) of patent invalidity or non-infringement or a “substantive determination that there is no cause of action for patent infringement or invalidity.”  Curiously, SA4361 also provides that any subsequent ANDA applicant that submits a “section viii” statement to an Orange Book-listed patent would be considered a “first applicant” eligible for 180-day exclusivity.

SA4361 and its predecessors appear to be rooted in a paper Apotex issued early last year.  In that paper, Apotex recommends that Congress work for legislation “that gives shared (if not sole) exclusivity to a generic challenger who, although not first to file a paragraph iv certification, is first to succeed in addressing the listed patents.”

By Kurt R. Karst –   

Since shortly after the enactment of the Hatch-Waxman Amendments in 1984, FDA has recognized an NDA sponsor’s ability to relinquish or selectively waive exclusivity, such as 5-year new chemical entity exclusivity and 3-year new use exclusivity, even though  the statute does not specifically permit relinquishment or waiver.  However, as FDA stated in a 2004 citizen petition response, it was not until 1997 that the Agency first considered an ANDA sponsor’s ability to relinquish or waive 180-day generic drug exclusivity.  In that 1997 case, which concerned a request from Genpharm to waive its pre-Medicare Modernization Act (“MMA”) 180-day exclusivity for Ranitidine HCl in favor of Granutec, FDA determined that a waiver was permissible.  That decision was challenged in court, see Boehringer Ingelheim Corp. v. Shalala, 993 F. Supp. 1 (D.D.C. 1997), and the D.C. District Court upheld FDA’s interpretation of the statute as permissible.  FDA subsequently proposed regulations (in 1999) to codify its interpretation, but those proposed regulations were withdrawn in 2002.  

FDA’s 2004 citizen petition response provides a comprehensive discussion of waiver and relinquishment of 180-day exclusivity.  Under FDA policy: 

an ANDA applicant who has obtained 180-day exclusivity may relinquish its exclusivity entirely or selectively waive the exclusivity in favor of a single ANDA, or multiple ANDAs, containing a paragraph IV certification.  Before the exclusivity period has been triggered, an applicant may only relinquish its exclusivity; after the exclusivity has been triggered, it may be selectively waived.

FDA stated in its petition response that “allowing eligible applicants to relinquish or waive [180-day] exclusivity enables them to exercise the exclusivity as they deem most beneficial,” and that there are four general reasons supporting waiver and relinquishment of 180-day exclusivity.  Specifically, that the practice of permitting relinquishment and waiver of 180-day exclusivity:

(1)  is based on a permissible statutory construction as acknowledged by the courts,
(2)  is consistent with the Agency’s long-standing allowance of waiver and relinquishment of other forms of market exclusivity,
(3)  promotes marketplace competition among pharmaceuticals in furtherance of the objectives of the [Hatch-Waxman Amendments], and
(4)  is consistent with FDA’s role in regulating the public health as opposed to competitive business arrangements.  

Importantly, FDA notes in its 2004 petition response that the Agency’s interpretation is limited to 180-day exclusivity subject to the pre-MMA (i.e., pre-December 8, 2003) statute:

[T]his response does not provide[] an Agency interpretation of section 505(j)(5)(B)(iv) as amended by the [MMA]. . . .  [T]he MMA made a number of changes to the statutory scheme in section 505(j) governing 180-day exclusivity, including providing tor forfeiture of the exclusivity. . . . The Agency has not yet assessed whether the changes made by the MMA should result in a different approach to waiver or relinquishment for those applications subject to the new exclusivity provisions.

Given the first applicant approach under the post-MMA statute, under which multiple first applicants can qualify for and share 180-day exclusivity (or forfeit such exclusivity), relinquishment and waiver of 180-day exclusivity is more complicated.

We are unaware of a post-MMA case in which a first applicant has relinquished 180-day exclusivity eligibility; however, FDA’s 2009 Letter Decision concerning generic versions of STARLIX (nateglinide) Tablets could provide some insight as to how FDA might ultimately address this issue in the context of multiple first applicants.  (Where there is only a single first applicant, relinquishment does not appear to complicate a 180-day exclusivity analysis.)  In the generic STARLIX case (see our previous post here), there were multiple first applicants and at least one first applicant forfeited 180-day exclusivity eligibility under FDC Act § 505(j)(5)(D)(i)(IV) (failure to obtain tentative approval in 30 months of ANDA submission).  FDA ruled that “a first applicant that forfeits exclusivity may obtain [ANDA] approval . . . and that first commercial marketing by any first applicant (including a first applicant that forfeits exclusivity) will begin the 180-day exclusivity period.”  Insofar as forfeiture is considered to be effectively the same as relinquishment, a first applicant that relinquishes its 180-day exclusivity could arguably continue to be a first applicant and not be blocked by another first applicant’s 180-day exclusivity eligibility, and also trigger other first applicants’ 180-day exclusivity. 

A selective waiver of 180-day exclusivity post-MMA (both where there is only a single first applicant and especially where there are multiple first applicants) is more complicated than relinquishment, as it confers on a subsequent applicant the most important benefit of first applicant status – 180-day exclusivity. 

We are aware of only one instance post-MMA in which FDA has permitted a selective waiver of 180-day exclusivity.  That case involved Bupropion HCl Extended-Release Tablets, 300 mg, and a single first applicant – Anchen Pharmaceuticals, Inc.  FDA approved Anchen’s ANDA No. 77-284 on December 14, 2006 and noted in the approval letter that as a first applicant the company is eligible for 180-day exclusivity.  Just a few days later, on December 15, 2006, however, FDA approved ANDA No. 77-415 for Bupropion HCl Extended-Release Tablets, 300 mg.  FDA noted in the approval letter for ANDA 77-415 that the applicant was not a first applicant but that there was a “relinquishment or selective waiver” of 180-day exclusivity by Anchen.  Although the ANDA approval letter is not clear on its face whether there was a relinquishment or waiver of 180-day exclusivity, the notation of exclusivity in the Orange Book for both applications makes clear that there was, in fact, a selective waiver and not a relinquishment.  (The Orange Book showed a period of shared 180-day exclusivity for both ANDAs.)

There is not, to our knowledge, a post-MMA case in which FDA has permitted a selective waiver of 180-day exclusivity where there are multiple first applicants.  Given the fact that FDA has permitted a waiver where there is a single first applicant, however, it seems likely that FDA, when faced with the issue, will permit a waiver when there are multiple first applicants.  But there will certainly be some ground rules. 

Being a first applicant means that you are the member of an exclusive club.  So to allow a non-member to share in the benefits of club membership, it seems possible that FDA would require all first applicants (whether 1 or 10) to agree in writing that a subsequent applicant should be accorded the benefits of club membership.  Also, it seems likely that because a subsequent applicant does not become a first applicant by virtue of all club members agreeing to a selective waiver, a first applicant will first have to trigger the 180-day exclusivity period before a waiver is made and a subsequent applicant can take advantage of the 180-day exclusivity period.    

The issue of selective waiver post-MMA is certain to crop up at some point in time, and we will be interested to see the outcome. 

By Ricardo Carvajal –

June 22 looms large on the calendar for firms subject to the requirements of the Family Smoking Prevention and Tobacco Control Act (“FSPTCA”) and FDA’s final rule curbing promotion and sale of cigarettes and smokeless tobacco to underage consumers.  In anticipation of that date, FDA has issued the following guidance documents:

• Compliance with Regulations Restricting the Sale and Distribution of Cigarettes and Smokeless Tobacco To Protect Children and Adolescents – This draft guidance document addresses questions raised by retailers with respect to their obligation under FDA’s final rule to ensure that cigarettes and smokeless tobacco are not sold to underage consumers.  It also addresses questions with respect to the obligation of retailers, distributors, and manufacturers to ensure compliance with advertising, marketing, and promotion restrictions imposed by that rule.  According to the document, FDA intends to exercise enforcement discretion with respect to certain requirements that are the subject of litigation (e.g., the limitation of labeling and advertising to black text on a white background and the restriction on the use of trade names of nontobacco products).  Violation of the final rule’s many other requirements could subject a retailer, distributor, or manufacturer to a range of civil and criminal penalties.  The final rule takes effect on June 22.

• Use of “Light,” “Mild,” “Low,” or Similar Descriptors in the Label, Labeling, or Advertising of Tobacco Products – This guidance document addresses the statutory ban on the use of the cited descriptors in labeling and advertising unless FDA authorizes such use.  Products labeled or advertised as such may not be sold after July 22 unless they were manufactured before June 22 and introduced into domestic commerce before July 22.

• Enforcement Policy Concerning Rotational Warning Plans for Smokeless Tobacco Products – This guidance document states FDA’s intent to exercise enforcement discretion with respect to the requirement that smokeless tobacco manufacturers, distributors, importers, and retailers have a rotational warning plan that has been approved by FDA, as long as they submit such a plan to the agency by July 22.  However, industry must begin rotating the warnings on June 22.

In addition, FDA has published “Harmful and Potentially Harmful Constituents” in Tobacco Products as Used in Section 904(e) of the Federal Food, Drug, and Cosmetic Act.  This draft guidance document provides FDA’s interpretation of the phrase “harmful and potentially harmful constituents.”  The FSPTCA requires that FDA publish a list of such constituents within two years of the law’s enactment.  That list will partially guide subsequent submissions by manufacturers of information on constituents in their products.  In that same vein, FDA will announce in the June 15 Federal Register that the Tobacco Product Constituents Subcommittee of the Tobacco Products Scientific Advisory Committee will meet on July 7-8 to "finalize its proposed list of harmful or potentially harmful constituents, the rational for inclusion of each substance, validated methods for measuring the constituents and the ancillary and normalization standards for the identified constituents."

By Kurt R. Karst –   

On the same day that the Senate Judiciary Committee held a hearing on “Oversight of the Enforcement of the Antitrust Laws,” at which Federal Trade Commission (“FTC”) Chairman Jon Leibowitz and U.S. Department of Justice (“DOJ”) Assistant Attorney General for the Antitrust Division Christine Varney testified (here and here) on, among other things, patent settlement agreements (what opponents call “pay-for-delay” agreements), Senators Herb Kohl (D-WI), Charles Grassley (R-IA), and Susan Collins (R-ME) proposed an amendment – SA 4332 – during the Senate’s consideration of the Tax Extenders Act (H.R. 4213) that could significantly curtail patent settlement agreements.  As we previously reported, H.R. 4213 is also being eyed as a vehicle for legislatively granting a patent term extension for U.S. Patent No. 5,196,404 covering The Medicines Company’s ANGIOMAX (bivalirudin).

SA 4332 appears to be identical to Sen. Kohl’s “Preserve Access to Affordable Generics Act” amendment, which was considered, but ultimately rejected, during debate of the Senate Health Care Reform Bill late last year.  That amendment was almost identical to the substitute amendment to S. 369, which was passed out of the Senate Judiciary Committee last year – see our previous post here. 

Like its predecessors, SA 4332 would amend the FTC Act to permit the FTC to “initiate a proceeding to enforce the provisions of [new Sec. 28] against the parties to any agreement resolving or settling, on a final or interim basis, a patent infringement claim, in connection with the sale of a drug product.”  Such agreements, if challenged, would be presumptively anticompetitive and unlawful unless it can be demonstrated “by clear and convincing evidence that the procompetitive benefits of the agreement outweigh the anticompetitive effects of the agreement.”  In addition, “[e]ach person, partnership or corporation that violates or assists in the violation of [new Sec. 28] shall forfeit and pay to the United States a civil penalty of not more than 3 times the gross revenue of the NDA holder from sales of the drug product that is the subject of the patent infringement claim for the period of the violation, starting with the date of the agreement.”  A summary of SA 4332 is available here. 

Senators Orrin Hatch (R-UT), Jon Kyl (R-AZ), John Cornyn (R-TX), and Tom Coburn (R-OK) previously criticized the legal presumption rule in S. 369.  A report on S. 369 issued earlier this year states that:

the bill would amount to a de facto per se ban on covered settlements—and would entail all of the evils attendant to a per se ban . . . . For a legal-presumption rule to work, however, the parties must be afforded a forum in which they can quickly and fairly test whether they have overcome the presumption and whether the agreement is valid.  Unfortunately, under the reported bill, settlements would be made presumptively unlawful, but the bill does not create a process for quickly resolving whether the agreement is unlawful.  The issue would not be resolved until the FTC brings an action to challenge the settlement, which could be years after the settlement was entered into.  Moreover, the current bill requires the brand and generic companies to rebut the presumption that the agreement is unlawful by clear and convincing evidence.  This is a heavy burden that is not appropriate for commercial litigation and that tilts the scales in a lawsuit sharply in the government’s favor. . . . By effectively preventing the parties from settling, it is likely that this bill will discourage generic drug companies from bringing challenges to brand companies’ patents in the first place—and as a result, the bill will ultimately reduce competition and raise prices for drugs that are currently subject to invalid or low-quality patents.

The introduction of SA 4332 comes on the heels of an April 2010 decision by a 3-judge panel of the U.S. Court of Appeals for the Second Circuit in In re: Ciprofloxacin Hydrochloride Antitrust Litigation.  As we previously reported, in that case, the Court affirmed a 2005 decision by the U.S. District Court for the Eastern District of New York to grant summary judgment for defendants (i.e., manufacturers of CIPRO (ciprofloxacin HCl) or generic versions of CIPRO) in an antitrust challenge to certain patent settlement agreements, but also invited further review of the case by the full Court, noting that “because of the ‘exceptional importance’ of the antitrust implications of reverse exclusionary payment settlements of patent infringement suits,” plaintiffs-appellants should petition for rehearing en banc.  Since issuing the decision, the Court has been petitioned for a rehearing en banc.  Several interested parties have filed amicus briefs in the case urging a rehearing by the full Court, including the FTC, DOJ, American Antitrust Institute, AARP/American Medical Association/The Public Patent Foundation, Inc., 34 State Attorneys General, AFSCME, and various consumer groups. 

The FTC is also appealing to the U.S. Court of Appeals for the Eleventh Circuit an April 2010 judgment related to a February 2010 order from the U.S. District Court for the Northern District of Georgia (Atlanta Division).  As we previously reported, in that case the district court largely dismissed multidistrict litigation brought by the FTC, direct purchasers, and indirect purchasers challenging certain agreements in which Solvay Pharmaceuticals, Inc. allegedly paid generic drug companies to delay generic competition to Solvay’s drug product ANDROGEL (testosterone gel). 

By Jeffrey N. Wasserstein –

Loyal readers of the FDA Law Blog have followed (with bated breath) the saga of Vermont’s law that prohibits pharmaceutical and medical device companies from giving many items that are permitted under the PhRMA Code and AdvaMed Code.  The plot has thickened even further with the recent passage of S. 88, which became law on May 27, 2010, albeit without the governor’s signature (he objected to some of the very provisions we’ll be discussing below). 

Most notably, the bill amends the existing law to provide that samples that may be given to patients include not only prescription items, but also over-the-counter drugs, nonprescription medical devices, or items of nonprescription durable medical equipment.  Nota bene:  “Sample” was also defined to include “starter packs and coupons or other vouchers that enable an individual to receive a prescribed product free of charge or at a discounted price.”  While permissible, the kicker here is that beginning on or before April Fools’ Day 2012, companies must disclose all samples that have been disseminated in Vermont during the prior calendar year, identifying for each sample the product, recipient, number of units, and dosage.  While pharmaceutical companies already track samples for purposes of compliance with the PDMA sample tracking requirements, the Vermont requirement also applies to coupons and vouchers for free or discounted prescription products, OTC products and nonprescription devices and DME which are not currently tracked.

The Vermont law does not apply by its terms to any samples required to be reported under the Patient Protection and Affordable Care Act of 2010 (a/k/a Healthcare Reform), which we summarized here, as long as the Vermont Attorney General determines that the U.S. Department of Health and Human Services ("HHS") will collect and report state- and recipient-specific information regarding samples.  How this will play out, remains to be seen. 

On the bright side, we have seen at various booths throughout the country at professional meetings and conferences signs that say “Dogs and Vermont Physicians Need Not Apply for Coffee”.  (Ok, we exaggerate slightly, but see below.) 

The new law clarifies that the provision of coffee or other snacks or refreshments at a booth at a conference or seminar is permitted, and does not even need to be reported!  Barristas from Bennington to Newport rejoice!

Other notable changes include permitting companies to provide grants for fellowship salary support, provided the manufacturer is completely hands-off, including that the institution requesting the grant selects the fellows, the manufacturer imposes no demands or limits on the use of the funds, and (demonstrating that Vermont doesn’t quite understand why companies might want to fund such fellowships), the fellowship cannot be named for the sponsoring manufacturer.  The law also clarifies that companies may sponsor continuing medical education programs and the sponsor may, in its discretion, use such funding to provide for meals and other food at the conference.  There was some  confusion prior to this law as to the permissibility of funding for CME where the CME provider used the funding for meals.  Clarity achieved!  Fund away!

We kid because we care.  As we noted in one of our prior posts on Vermont, states are free to experiment.  At some point, the experimentation goes too far.  As noted by the Governor of Vermont in his statement explaining why he was refusing to sign the bill and was allowing it to become law without his signature, “physicians, non-profits and other organizations across Vermont have expressed significant concern about the chilling effect certain provisions could have on the ability of low-income Vermonters to receive free samples of vital prescription drugs.”  At some point, companies will weigh the cost of doing business in Vermont and decide that it isn’t worth it.  Or, they will do business and decide it’s not worth providing coupons, vouchers or samples to physicians in Vermont, thereby avoiding the hassle of reporting to the Vermont Attorney General.  That cannot be good for Vermont patients, as noted by Governor Jim Douglas.  But at least we know companies can give Vermont MDs a cup of joe at the next professional meeting.

By Kurt R. Karst –   

FDA's recent approval of an ANDA submitted by Perrigo R&D Company ("Perrigo") for a generic version of the over-the-counter drug MONISTAT 1 Combination Pack (1200 mg miconazole nitrate vaginal insert and 2% miconazole nitrate cream) contains some interesting language concerning 180-day exclusivity eligibility.  It it the latest type of post-Medicare Modernization Act ("MMA") 180-day exclusivity "punt" language adopted by FDA. 
 
As we previously reported, FDA has, on several occasions punted on the issue of post-MMA 180-day exclusivity eligibility.  Those punts have come up in the context of 180-day exclusivity forfeiture under FDC Act § 505(j)(5)(D)(i)(IV), where a company failed to obtain tentative ANDA approval within 30-months of application submission.  In each of those cases, FDA did not make a formal forfeiture determination at the time of ANDA approval and stated it would do so only if another applicant becomes eligible for approval within 180 days after exclusivity is triggered.
 
The latest punt comes under the failure-to-market forfeiture provisions at FDC Act § 505(j)(5)(D)(i)(I), which provide that 180-day exclusivity is forfeited based on the "later of" two dates: (1) the earlier of 75 days after ANDA approval or 30 months after ANDA submission; and (2) 75 days after which "[t]he patent information submitted under [FDC Act § 505(b) or (c)] is withdrawn by the holder of the" NDA holder (FDC Act § 505(j)(5)(D)(i)(I)(bb)(CC)), among two other litigation-related events (FDC Act § 505(j)(5)(D)(i)(I)(bb)(AA) & (BB)).  In March 2010, the U.S. Court of Appeals for the District of Columbia Circuit ruled in Teva Pharms USA, Inc. v. Sebelius, 595 F.3d 1303 (D.C. Cir. 2010), that Teva did no forfeit 180-day exclusivity eligibility under the failure-to-market forfeiture provisions at FDC Act § 505(j)(5)(D)(i)(I), and FDC Act § 505(j)(5)(D)(i)(I)(bb)(CC) in particular.  In doing so, the Court reasoned that the patent delisting counterclaim provision at FDC Act § 505(j)(5)(C)(ii)(I) added by the MMA must be read together with the patent delisting forfeiture provision at FDC Act § 505(j)(5)(D)(i)(I)(bb)(CC), and that FDA's broad reading of FDC Act § 505(j)(5)(D)(i)(I)(bb)(CC), in which the Agency interpreted the provision such that the mere request to withdraw patent information from the Orange Book is a forfeiture event under FDC Act § 505(j)(5)(D)(i)(I)(bb)(CC), was not sustainable.  FDA has been reluctant to adopt a narrow interpretation of FDC Act § 505(j)(5)(D)(i)(I)(bb)(CC), but has done so nevertheless. 
 
MONISTAT 1 Combination Pack is listed in the Orange Book with two patents – U.S. Patent Nos. 5,514,698 ("the '698 patent) and 6,153,635 ("the '635 patent").  Both patents are identified with a "Delist Requested" flag, which first appeared in the May 2009 Orange Book Cumulative Supplement.  According to FDA's Paragraph IV Certification List, FDA received Perrigo's ANDA containing a Paragraph IV certification to the '698 and '635 patents on December 5, 2007.  This set up a potential 180-day exclusivity forfeiture under FDC Act § 505(j)(5)(D)(i)(I) for late last week, as the "later of" date was 30 months after ANDA submission.  FDA timely approved Perrigo's ANDA, however, and stated in the approval letter that:

With respect to 180-day generic drug exclusivity for Miconazole Nitrate Vaginal Insert (1200 mg) and Miconazole Nitrate Cream (2%), Perrigo was the first ANDA applicant to submit a substantially complete ANDA for Miconazole Nitrate Vaginal Insert (1200 mg) and Miconazole Nitrate Cream (2%), with a paragraph IV certification to the patents listed above.  Therefore, with this approval, Perrigo may be eligible for 180 days of generic drug exclusivity for Miconazole Nitrate Vaginal Insert (1200 mg) and Miconazole Nitrate Cream (2%). . . .   The agency notes that a delisting request has been submitted for the '698 and '635 patents.  The agency is not making a formal determination at this time of Perrigo's eligibility for 180-day generic drug exclusivity.  It will do so only if another applicant becomes eligible for approval within 180 days after Perrigo begins commercial marketing of Miconazole Nitrate Vaginal Insert (1200 mg) and Miconazole Nitrate Cream (2%). [(emphasis added)]

Now, someone could read the emphasized language above and conclude that FDA has not fully embraced the Teva decision.  After all, there has not, to our knowledge, been a counterclaim brought under FDC Act § 505(j)(5)(C)(ii)(I) that would call Perrigo's 180-day exclusivity into question.  So why even include the "punt" language in the approval letter at all?  We think that FDA included the language in the letter to cover all of the bases.  That is, as a placeholder just in case a counterclaim is brought by another applicant under FDC Act § 505(j)(5)(C)(ii)(I). 

By Diane B. McColl & Ricardo Carvajal –

It’s here!  FDA’s Center for Veterinary Medicine (“CVM”) finally implemented a "generally recognized as safe" (“GRAS”) notification program for use of ingredients in animal feed or pet food.  We have waited for this program since 1997, when it was first proposed along with FDA's Center for Food Safety and Applied Nutrition's (“CFSAN's”) GRAS notification program for human food ingredients.  CVM's efforts to establish the program were announced more than a year ago.  In the ensuing months, producers of potential new ingredients met with CVM, trying to understand how the program might work.  Now we have a basic framework.  CVM's GRAS notification program food parallels CFSAN's GRAS notification program, which has operated successfully for more than 10 years.  As CFSAN did in the early days of its program, CVM “strongly encourages” potential notifiers to discuss their plans with the Division of Animal Feeds prior to submission.

Based on CVM’s Federal Register notice and the instructions provided on its website, it appears that CVM intends to administer its program so that it is both substantively and procedurally consistent with CFSAN’s program -  with a couple of notable exceptions.  First, if the ingredient will be fed to food-producing animals, safety of the ingredient must be shown   both for target animals consuming the ingredient and for humans consuming food derived from those animals.  Thus, for both the target animal and the human populations, a GRAS notifier must establish that the proposed use of a food ingredient is not just safe, but also generally recognized as such.  Second, CVM describes its program as a “pilot” program, and notes that resources are limited in the animal food program.  Consequently, CVM does not commit to a specific time frame for responding to notifications.  While CFSAN originally set a target of 90 days for its GRAS notifications, that target has crept up to 180 days.

As with CFSAN’s program, notifiers under CVM’s program should expect their GRAS determination claims to become publicly available on the date that the GRAS notice is received.  Pivotal safety data and information (i.e., those data without which the GRAS determination cannot stand) should already be in the public domain.  Other data and information in the GRAS notice will immediately be made available to the public, subject to exemptions in FDA’s regulations implementing the Freedom of Information Act (21 C.F.R. Part 20).

By Ricardo Carvajal –

Kellogg Company has agreed to FTC’s expansion of the settlement order that the company entered into in July 2009 regarding false claims that Frosted Mini-Wheats improve children’s attention (see our prior post here).  At issue now are “dubious health claims” that Rice Krispies supports children’s immunity.

Under the modified order, Kellogg is prohibited from making any representation in connection with the marketing of any food regarding

A. the benefits, performance, or efficacy of such product for cognitive
function, cognitive processes, or cognitive health; or

B. any other health benefit of such product

unless the representation is not misleading and is adequately substantiated.  The modified order now describes FTC’s substantiation standard in detail.  Kellogg must have:

competent and reliable scientific evidence that is sufficient in quality and quantity based on standards generally accepted in the relevant scientific fields, when considered in light of the entire body of relevant and reliable scientific evidence, to substantiate that the representation is true. . .. [C]ompetent and reliable scientific evidence means tests, analyses, research, or studies that have been conducted and evaluated in an objective manner by qualified persons and are generally accepted in the profession to yield accurate and reliable results.

As we noted in a prior posting, FTC staff have repeatedly expressed concern over the use of immunity claims in promotion for foods.  However, the claim used by Kellogg (“now helps support your child’s immunity”) strikes us as relatively timid – notwithstanding the Commission’s characterization of it as a claim to “boost” immunity.  Although FTC’s action might be partially attributable to the fact that Kellogg embarked on its immunity campaign shortly after negotiating the original settlement, it appears that the Commission is prepared to challenge any questionable immunity claim – even those that don’t explicitly reference an ability to boost immunity.

By Kurt R. Karst –

Earlier this year, the U.S. Patent and Trademark Office (“PTO”) denied an application for a Patent Term Extension (“PTE”) for U.S. Patent No. 6,869,939 (“the ‘939 patent”).  The ‘939 patent is one of four patents listed in FDA’s Orange Book as covering NEXTERONE (amiodarone HCl) Injection, which FDA approved in December 2008 under New Drug Application (“NDA”) No. 22-325. 

Amiodarone has been around for a while.  It was first approved in December 1985 as CORDARONE under NDA No. 18-972.  So it was no surprise when the PTO, in March 2010, denied a PTE for the ‘939 patent based on an analysis of the “first permitted commercial marketing” criterion in the PTE statute. 

Under 35 U.S.C. § 156(a)(5)(A), the term of a patent claiming a drug shall be extended from the original expiration date of the patent if, among other things, “the permission for the commercial marketing or use of the product . . . is the first permitted commercial marketing or use of the product under the provision of law under which such regulatory review period occurred” (emphasis added).  The term “product” as used in § 156(a)(5)(A) is defined in § 156(f)(1) to mean “drug product,” which is defined in § 156(f)(2) to mean the “active ingredient of (a) new drug, antibiotic drug, or human biological product . . . including any salt or ester of the active ingredient, as a single entity or in combination with another active ingredient.”  The FDA’s PTE regulation at 21 C.F.R. § 60.3(b)(2) defines the term “active ingredient” to mean:

any component that is intended to furnish pharmacological activity or other direct effect in the diagnosis, cure, mitigation, treatment, or prevention of disease, or to affect the structure or any function of the body of man or of animals.  The term includes those components that may undergo chemical change in the manufacture of the drug product and be present in the drug product in a modified form intended to furnish the specified activity or effect.

Although the PTO had historically defined the term “product” in 35 U.S.C. § 156(a)(5)(A) to mean “active moiety” (i.e., the molecule in a drug product responsible for pharmacological action, regardless of whether the active moiety is formulated as a salt, ester, or other non-covalent derivative) rather than “active ingredient” (i.e., the active ingredient physically found in the drug product, which would include any salt, ester, or other non-covalent derivative of the active ingredient physically found in the drug product), in May 2010, a 3-judge panel of the U.S. Court of Appeals for the Federal Circuit ruled in two cases – Photocure ASA v. Kappos and Ortho-McNeil Pharmaceutical, Inc. v. Lupin Pharmaceuticals, Inc. (here and here) – that the “active ingredient” interpretation of the statute is the proper interpretation.  (See our previous post here.)

The PTO’s denial of a PTE for the ‘939 patent is based on a straightforward analysis:

It is undisputed that amiodarone hydrochloride is the active ingredient of Applicant’s NEXTERONE® drug product. . . .  It is also undisputed that amiodarone hydrochloride was approved by the FDA under section 505 of the FFDCA prior to the December 24, 2008 approval of NEXTERONE®. . . .  Accordingly, the later approved NEXTERONE® (amiodarone hydrochloride) does not represent the first permitted commercial marketing or use of the “product” under the provision of law under which such regulatory review occurred.

The PTO next turns its attention to two curious statements in the PTE application – namely that NEXTERONE “is a sulfobutyl ether ß-cyclodextrin-amiodarone hydrochloride intravenous solution,” and that “[t]he sulfobutyl ether -cyclodextrin-amiodarone hydrochloride complex was not previously approved prior to the approval of NEXTERONE®.”  The PTO’s response is that these statements are irrelevant for purposes of § 156(a)(5)(A):

[A]s already stated, it is undisputed that amiodarone hydrochloride is the active ingredient of Applicant’s NEXTERONE® drug product.  The sulfobutyl ether ß-cyclodextrin component is not identified as an active ingredient of NEXTERONE® by the electronic Orange Book.  Indeed, the PTE Application itself does not identify sulfobutyl ether ß-cyclodextrin as an active ingredient of NEXTERONE®.  Accordingly, whether sulfobutyl ether ß-cyclodextrin-amiodarone hydrochloride complex has been previously approved prior to the approval of NEXTERONE® is irrelevant to the determination of whether the requirement of section 156(a)(5)(A) has been fulfilled.

The PTE applicant recently filed a Request for Reconsideration of the PTO’s denial of a PTE for the ‘939 patent “on the grounds that NEXTERONE® represents the first permitted commercial marketing or use of the Nexterone ‘product,’ sulfobutyl ether ß-cyclodextrin-amiodarone hydrochloride complex. . . .”  According to the PTE applicant:

The identification of “amiodarone hydrochloride” . . . was simply to indicate that amiodarone hydrochloride provides the pharmacological activity of the drug product.  It was the intention of Applicants to convey that the “active ingredient” in the drug product NEXTERONE® is the sulfobutyl ether ß-cyclodextrin amiodarone hydrochloride complex.

Because the definition of “active ingredient” at 21 C.F.R. § 60.3(b)(2) includes components that are “present in the drug product in a modified form intended to furnish the specified activity or effect,” and because, according to the PTE applicant, “amiodarone forms an inclusion complex with sulfobutyl ether-ß cyclodextrin,” and the  ‘939 patent “describes the interaction between amiodarone and sulfobutyl ether-ß cyclodextrin resulting in a complex in which the amiodarone is ‘part of a clathrate or inclusion complex,’”  “sulfobutyl ether-ß cyclodextrin amiodarone hydrochloride complex” is the active ingredient in NEXTERONE and the “drug product” under 35 U.S.C. § 156(f)(2).  FDA has not previously approved “sulfobutyl ether-ß cyclodextrin amiodarone hydrochloride complex,” so the approval of NEXTERONE would, according to the PTE applicant, meet the first permitted commercial marketing or use PTE criterion at 35 U.S.C. § 156(a)(5)(A).

The PTO typically holds firm to its PTE denials, so it seems unlikely that the Office will reverse the ‘939 PTE denial in light of the reconsideration request.  If that is the case here, then it is possible that more PTE litigation will be on the way.  Stay tuned!

 By Kurt R. Karst –   

Last week’s 29-page decision by the U.S. District Court for the Eastern District of Pennsylvania in In re Budeprion XL Marketing & Sales Litigation is yet more affirmation that lower courts are broadly reading and applying the U.S. Supreme Court’s 2009 decision in Wyeth v. Levine.  In Levine, the Court ruled, by a 6-3 vote, in the context of a  brand name drug, that FDA labeling approval does not preempt state laws.  Since that decision, myriad courts have taken up the issue of preemption doctrine as it applies to generic drugs (generally ruling against preemption), and the U.S. Supreme Court recently invited the Solicitor General to express the views of the United States on the topic (see our previous post here). 

In re Budeprion XL Marketing & Sales Litigation is a putative nationwide class action brought under California state consumer protection laws (i.e., California’s Unfair Competition Law and Consumer Legal Remedies Act) in which the plaintiffs allege that certain manufacturers of generic versions of the antidepressant WELLBUTRIN XL (bupropion HCl) Extended-Release Tablets failed to warn them about differences between their generic and the brand name drug, and that such differences caused undesirable effects.  According to the court, “[t]hese generics use a matrix technology rather than a membrane-release technology and rely on the size of the pill to control the release of the medication.”  As such, “[t]he generics subject to this litigation achieve peak concentrations in two hours, versus five hours for Wellbutrin XL . . . .  Plaintiffs say the more rapid release of Defendants’ drugs renders them less effective in treating depression and more dangerous than those products using a membrane-release technology.”  As we previously discussed, generic and brand name drugs can differ in release mechanism and still be therapeutic equivalents, provided the products are pharmaceutically equivalent and are demonstrated to be bioequivalent. 

In the bupropion class action, the plaintiffs contend that post-ANDA approval the generic manufacturers had a duty to disclose the differences between their products and the brand name drug by amending their labeling through FDA’s Changes Being Effected regulations.  The defendants argue in their Motion to Dismiss that “plaintiffs now directly challenge the exclusive role Congress assigned FDA to accomplish the Hatch-Waxman Act’s objectives,” and that the plaintiffs’ claims are preempted by the FDC Act and FDA’s determination that the generic WELLBUTRIN XL drug products are bioequivalent to the reference listed drug:

Recognizing the conflict between their claims and FDA’s equivalence determination, plaintiffs have tried to label their case as one about a “failure to warn.”  But this is not a personal injury case where a plaintiff seeks damages for injuries resulting from an undisclosed risk that FDA never considered or ruled on.  And none of the “failure to warn” cases concerns alleged differences between a brand and a generic product.  Here, plaintiffs’ fundamental complaint is with FDA’s decision to approve the Generic Products and allow them to remain on the market as equivalents of Wellbutrin XL.  If Plaintiffs’ allegations were right, and the Generic Products were not as safe and effective as the brand drug, then FDA could not allow the Generic Products to remain on the market as generic equivalents.  21 U.S.C. § 355(e).  Plaintiffs, however, seek to impose state-law obligations purportedly requiring defendants to disclose certain differences between the Generic Products and Wellbutrin XL, even though FDA has necessarily determined that all those differences are immaterial.  Requiring such representations would conflict directly with FDA’s determination that, as an equivalent generic, the Generic Products are “the same as a brand-name drug in: dosage, safety, strength, quality, the way it works, the way it is taken, and the way it should be used.”

And with respect to the applicability of the Levine decision, the generic drug manufacturers note that “[t]his is not a case where FDA has not ‘made an affirmative decision’ about the issue in dispute. . . .  Rather, FDA has addressed the exact issues raised by plaintiffs in finding the Generic Products to be bioequivalent to Wellbutrin XL and approving them for marketing.”  Moreover:

Were plaintiffs to prevail, FDA approval of a generic as bioequivalent would no longer be enough and generic drug manufacturers would have to engage in the very kind of safety and efficacy testing that the Hatch-Waxman Act expressly rejects for generic drug approval.  The result is undeniable: there would be fewer generic drugs developed for approval by FDA. . . .  The use of state law to second-guess FDA’s determination that the Generic Products are as safe and effective as Wellbutrin XL unquestionably would undermine Congress’s express delegation of exclusive authority to FDA to select the methods and standards for approving generic products as interchangeable with brand products, and discourage the marketing of approved products.  Such an application of state law is, thus, preempted.

The court (Judge Berle M. Schiller) was not persuaded and denied the defendants’ Motion to Dismiss.  “[T]he argument that Congress would permit state law to apply to the labeling of name brand drugs but would preempt state law actions against generic drug makers is a tough pill to swallow,” according to Judge Schiller, and “[t]he reasoning in Levine applies equally well to generic drugs.”  Central to Judge Schiller’s decision are fourt points:

• First, a generic drug manufacturer is not absolved of liability because the FDA has approved its generic product.  The Hatch-Waxman Act allows generic drug makers to expeditiously get their products to market – it does not allow generic drug makers to wash their hands of any responsibility for monitoring the safety and efficacy of their drugs once sold.

• Second, preemption is not to be lightly applied, particularly in this case because the field of law is one in which states have historically played a role.  Defendants have not pointed to any evidence of clear Congressional intent to preempt Plaintiffs’ claims, instead retracing arguments other courts have rejected. . . .   Furthermore, Plaintiffs would be left without a remedy if their state-law claim were preempted. Defendants need to posit more than the FDA’s bioequivalence determination to show that Congress meant to leave those injured by generic drug makers unable to seek redress for their injuries.

• Third, Levine leaves it beyond doubt that ultimate responsibility for the labeling of drugs remains with the maker of the drug, not the FDA.

• Fourth, although Defendants repeatedly assert that this is a case in which the FDA has already spoken and therefore a jury may not reassess the position taken by the FDA, that fact, even if correct, would not render Plaintiffs’ claims preempted. . . .  Federal laws and regulations do not leave generic drug makers impotent upon learning that their labels are inadequate or that their medication causes adverse side effects that must be reported. Generic drug makers may add or strengthen warning labels, even without prior FDA approval.

It is unclear whether the generic defendants in the case will appeal Judge Schiller’s decision.  Given the “Levine-creep” (the preemption version of “bio-creep”) that this decision represents, however, in which one has to ask what facts would, in fact, support Levine preemption, an appeal certainly seems like a possibility. 

By Ricardo Carvajal & Diane B. McColl –

The Alliance for Natural Health (“ANH”) has prevailed on summary judgment in its court challenge to FDA’s denials of, and restrictions on, certain qualified health claims regarding selenium and cancer.  The decision marks the latest chapter in a long-running battle between industry and FDA over the agency’s attempts to implement the FDC Act’s restrictions on the use of health claims in the labeling of foods, including dietary supplements. 

ANH submitted a qualified health claim ("QHC") petition to FDA which proposed numerous claims that consumption of selenium reduces the risk of some cancers.  The court’s conclusions with respect to FDA’s handling of those claims are summarized below. 

• FDA denied as “misleading on their face” claims that selenium “may reduce the risk of certain cancers” and “may produce anticarcinogenic effects.”  FDA argued that the former claim is misleading because it fails to specify the cancers on which selenium has an effect, and that the latter claim falsely implies that selenium has an effect on all cancers.  Citing the principles established in Pearson I (Pearson v. Shalala, 164 F.3d 650, 652 (D.C. Cir. 1999)), the court found FDA’s action unconstitutional in the absence of “empirical evidence that any disclaimer would fail to correct the claims’ purported misleadingness.”  If FDA cannot produce that evidence, then FDA must draft “one or more” disclaimers for those claims. 

• FDA denied a claim regarding lung/respiratory tract cancers and a claim regarding colon/digestive tract cancers on the ground that the claims were unsupported by any credible evidence.  The court conducted its own review of the underlying studies and found that FDA’s basis for discounting one or more of the studies was erroneous and not in keeping with its guidance on the evaluation of health claims.  For the lung/respiratory tract cancer claim, FDA must now draft a disclaimer that accounts for the one study deemed by the court to be supportive.  For the colon/digestive tract claim, FDA must reconsider that claim and draft a disclaimer as needed.  

• FDA entirely redrafted a claim regarding prostate cancer because the agency found the language proposed by plaintiff to be false and misleading.  The court concluded that FDA erred when it “completely eviscerated plaintiff’s claim” instead of taking the less restrictive approach of drafting one or more “short, succinct, and accurate” disclaimers.  Further, based on its review of the underlying studies, the court found FDA’s proposed claim to be contradictory and inaccurate.

Barring a successful appeal, this decision could cement in place a regime for FDA’s review of qualified health claims that is very favorable to health claim petitioners.  As a practical matter, the burden that FDA would have to meet before it can deny a qualified health claim petition would be unachievable in all but the most extreme cases – an outcome that should cheer advocates of unfettered commercial speech.

Although qualified health claims and structure/function claims are governed by different standards, this decision could raise questions with regard to whether the government’s current approach to substantiation of structure/function claims can withstand a First Amendment challenge.  FDA and FTC guidance documents maintain that there is no fixed substantiation standard for such claims; however, both agencies have suggested that a minimum of two high quality clinical studies are needed.  Query whether either agency could lawfully suppress an appropriately qualified structure/function claim that is based on a single study – or any other credible scientific evidence, for that matter.

Although individual firms should certainly profit from a less restrictive approach to the use of health and structure/function claims, there is a risk to industry writ large.  If the end result is an explosion in the use of claims based on very limited scientific support, and if those claims prove to have no merit in the long run, then consumers’ skepticism of all health-related claims can be expected to increase.  This would be an “unhappy meal” indeed.

By Susan J. Matthees –

FDA has denied a Citizen Petition requesting that FDA require drug and device companies to submit data only from non-animal test methods ("NATMs") whenever NATMs are available.  The Citizen Petition was submitted on behalf of the Mandatory Alternatives Petition Coalition (the Coalition) in 2007.  In April we reported that the Coalition had sued FDA to force the Agency to substantively respond to the Citizen Petition. 

In the denial letter, FDA explained that although the Agency shares the goal of reducing reliance on animal testing, there are currently no suitable non-animal alternatives to the testing necessary for FDA to conclude that a drug or device is safe for human use.  However, FDA stated that it intends to publish a draft guidance on the use of NATMs to “aid refinement, reduction and replacement of animal tests whenever feasible by explicitly encouraging sponsors to approach the Agency early in the development process for consultation on the suitability and acceptability of non-animal tests.”  FDA also reminded the Coalition that the Agency currently accepts a NATM where the NATM provides information that is equal to the equivalent animal testing method. 

FDA responded to each of the Coalition’s five requests in detail, mentioning several times that it “carefully considered” the particular issues.  FDA acknowledged that the Coalition is correct that animal testing models sometimes fail to predict safety risks in humans (e.g., Vioxx and HIV protease inhibitors), but explained that testing in animals is still the most reliable method for studying the safety of a drug.  FDA also stated several times that the Agency is open to recommendations for reliable NATMs and will consider any new NATMs that could provide data equal to animal testing. 

By William T. Koustas –

As we have previously reported (here, here, and here), the FTC has delayed enforcement of its Red Flags Rule (“the Rule”) several times since its original effective date of November 1, 2008.  Now, some in Congress have requested that the FTC again delay enforcement while Congress takes up legislation that would more precisely define the entities covered by the Rule.  As a result, the FTC has delayed the Rule’s enforcement until December 31, 2010, unless Congress passes legislation with an earlier effective date.