By Kurt R. Karst –      

Over the past several weeks there has been growing chatter about FDA’s Document Archiving, Reporting and Regulatory Tracking System (“DARRTS”) and how its implementation might affect generic drugs.  DARRTS is a Center for Drug Evaluation and Research (“CDER”) information technology platform developed to replace many of CDER’s core tracking systems, including those for ANDAs.  Earlier this year, FDA issued a Manual of Policies and Procedures (“MaPP”) – MaPP 6700.4 – on the use of DARRTS for systematically tracking post-market drug safety issues, which explains that “[u]ltimately, [DARRTS] will be the archival system of record for new drug applications (NDAs), biologics license applications (BLAs), and abbreviated new drug applications (ANDAs) . . . .”  Another MaPP, issued in April 2009 – MaPP 5210.3 – discusses the use of DARRTS in the Office of Generic Drugs’ (“OGD’s”) documentation of bioequivalence study reviewer productivity.

As DARRTS implementation moves forward, we understand that it will be used to, among other things, drive ANDA review priority based on a points system.  Point values may be assigned to an ANDA based on an overview of patent certifications and when an application may be eligible for final approval or tentative approval, as well as once a particular OGD review component (e.g., chemistry or bioequivalence) is completed.  The greater the number of points, the higher the application moves in the review queue.  The intent of using this new point system is reportedly to make more efficient use of OGD’s resources so that those applications that can or should be approved sooner than others will be prioritized over applications that might not be approved for several years (e.g., because an ANDA contains a Paragraph III Certification to a patent that expires in many years). 

Another effect of DARRTS implementation will be to create a new application numbering system.  For decades, FDA has used a numeric system that easily identifies an application as an NDA or ANDA.  For example, applications with a 20,000 or 50,000 series number are NDAs, and applications with a 70,000 or 90,000 series number are ANDAs.  Under DARRTS, however, all submissions will now be numbered sequentially beginning with 200,000 regardless of application type.  This change was recently criticized in a docket submission from a former FDA official:

The usefulness of being able to identify the type of application ANDA or NDA from the application number cannot be overstated.  This will no longer be possible unless this is reevaluated and changed by FDA.  The IT folks at FDA should serve the programs and cater to program needs not the other way around.  This is vital historical information and is very useful to industry to be able to quickly identify NDA or ANDA filings for planning, patent and other purposes.  The transparency has now been lost on this issue.

There is still much that is unknown about how DARRTS will be rolled out in OGD.  Perhaps FDA will explain these changes at an upcoming conference or in an announcement. 

By Carrie S. Martin –

On September 21, 2009, FDA announced in a Federal Register notice that the Agency plans to hold a public hearing to discuss issues regarding the promotion of FDA-regulated products – specifically prescription drugs, prescription biologics, and medical devices – via the Internet and social media.  Many in industry feel that guidance from FDA on this issue is long overdue.  

The meeting is intended to help FDA form its policy on the promotional of these products using the Internet and social media tools.  Of particular interest to the Agency is how “Web 2.0” can be used to promote products in a truthful, non-misleading, and balanced manner to both consumers and health care professionals (“HCPs”).  Web 2.0 includes new web development and design that facilitates interactive information sharing, such as social-networking sites (e.g., Facebook, Sermo), video-sharing sites (e.g., YouTube), wikis (e.g., Wikipedia), podcasts, blogs, and micro-blogs (e.g., Twitter).  The hearing will not address nonprescription drug promotion.

FDA invites comments on the “general concept” of Internet promotion, any particular aspect of Internet promotion, and the following questions: 

(1)    For what online communications are manufacturers, packers, or distributors accountable?  More specifically: 

• What criteria should be applied to determine when third-party communications are subject to substantive influence by companies that market products related to the communications/discussions?
• When should third-party discussions be treated as being performed by, or on behalf of, the companies that market the product?
• How should companies disclose their involvement or influence over discussions or material?
• Are there different considerations that should be weighed depending on the specific social media platform that is used or based on the intended audience?
• What is the experience to date with company communications being altered by third-parties? 

(2)    How can manufacturers, packers, or distributors fulfill regulatory requirements (e.g., fair balance) in their Internet and social media promotion, especially when some tools have space limitations or allow for real-time communications?  More specifically: 

• How should product information be presented to ensure that the user has access to a balanced presentation of risks and benefits?
• Are there data to support whether different types or formats of presentations have an impact on the public health?
• Are there ways to address regulatory concerns associated with space limitations or tools that allow for real-time communications to present product information?
• How should companies address the potential volume of information shared on various social media sites with regard to real-time information that is continuously posted and regulatory requirements to submit promotional materials to FDA as applicable?

(3)    What parameters should apply to the posting of corrective information on Web sites controlled by third-parties?  More specifically:

• Is there any data or research on how companies have approached these issues?
• Are there any criteria that could be used to determine how to correct misinformation on a Web site outside a company’s control?
• Should the parameters differentiate the prominence of the third-party site, its intended audience, its intended purpose, and/or the author of the information on the site?

(4)    When is the use of the links appropriate?  More specifically:

• What are appropriate techniques regarding the use of links (including between various social media tools) and is there data about whether or not users find these approaches to be misleading?
• Should parameters be established for links to and from Web sites?
• Is there data regarding how often users click on different categories of links (e.g., banner ads, sponsored links, organic search result links) to get additional information about products?

(5)    Questions specific to Internet adverse event reporting, including:

• How are entities with post-marketing reporting responsibilities using the Internet and social media tools to monitor adverse event information?
• How is adverse event information from these sources being received, reviewed, and processed?
• What challenges are presented in handling adverse event information from these sources?
• What uncertainties are there regarding what should be reported from these sources to meet FDA adverse event reporting obligations?

The meeting is scheduled for November 12 and 13, 2009 (8 a.m. to 5 p.m. each day) at the National Transportation Safety Board Conference Center in Washington, D.C.  Registration is required and must be submitted by October 9, 2009.  Participation will be determined on a first-come, first-served basis. 

To register or submit written comments, use the following address:  Division of Dockets Management (HFA305), Food and Drug Administration, 5630 Fishers Lane, Rm. 1061, Rockville, Maryland 20852.  Electronic registration and comments may be submitted via www.regulations.gov.  FDA will accept public comments through February 28, 2010. 

By Kurt R. Karst –      

A few months ago after FDA’s approval of an NDA for the Pancreatic Enzyme Product (“PEP”) CREON (pancrelipase) (amylase; lipase; protease) we queried whether FDA might apply a presumption in favor of New Chemical Entity (“NCE”) status for all PEPs, such that each drug would be granted a 5-year period of exclusivity.  There seemed to be good reason to conclude that FDA would presume NCE status for each PEP; however, it was not until earlier this week that FDA made public its exclusivity decision.

FDA stated its “presumption in favor of NCE status” policy in 2005 in the context of the Agency’s approval of various non-recombinant hyaluronidase drug products.  In the case of hyaluronidase, uncertainty arose from the fact that such drug products are complex proteins that are not fully characterized.  FDA stated that:

Generally, if the Agency has insufficient information to know whether a product contains a previously approved active moiety, the applicant would be required to submit an NDA containing substantial clinical safety and efficacy data.  These data requirements could reasonably be expected to be comparable to those that would be needed for approval of an NCE.  Under the presumption, if it is not known whether a product contains a previously approved active moiety, the product also would be treated as an NCE for marketing exclusivity purposes, and, accordingly, granted 5-year exclusivity.  [(emphasis added)]

In the case of PEPs, FDA had previously stated that given their complexity “it is unlikely that currently available physiochemical and biological analytical tools would be able to demonstrate that the active ingredients in [PEPs] from two different manufacturers are the same.”  So, when FDA approved another PEP in August 2009 – ZENPEP (pancrelipase) (amylase; lipase; protease) – it stood to reason that FDA determined that both recently approved PEPS – CREON and ZENPEP – would each be granted 5 year exclusivity in accordance with FDA’s “presumption in favor of NCE status” policy.  But it was not until FDA published its latest Orange Book Cumulative Supplement (pages A-32-33) that the decision to grant NCE exclusivity with respect to each product became public. 

There are still pending at FDA a couple of decisions concerning NCE exclusivity, including for VERAMYST (fluticasone furoate) Nasal Spray and VYVANSE (lisdexamfetamine dimesylate) Capsules.  FDA is expected to issue a ruling concerning VYVANSE later this month.

By Alan M. Kirschenbaum –

Today the Senate Finance Committee (“SFC”) released the Chairman’s Mark of the “America’s Healthy Future Act of 2009,” which currently is scheduled for Committee mark up next Tuesday, September 22.  Among the various health reform proposals in the House and Senate, the Senate Finance Committee bill is viewed as the approach most likely to succeed.  Although health care reform will substantially benefit drug and device manufacturers by increasing the insured population, the bills also seek to extract discounts from manufacturers to help pay for reform.  The SFC Chairman’s Mark is no kinder to manufacturers in this regard than the health care reform bill reported out of the House Energy and Commerce Committee on July 31, which was the subject of an earlier post. 

Both the SFC Chairman’s Mark and the House bill would increase the minimum Medicaid rebate, though the Mark would increase it more than the House bill, and, unlike the House bill, would impose increases on non-innovator as well as innovator drugs.  Other, more minor tweaks to the Medicaid Rebate Program are similar.  Both would change the Federal Upper Limit methodology, though the FULs in the Senate version would be higher.  Both bills would also require drug manufacturers to fund a 50 percent discount on drugs purchased by Medicare Part D beneficiaries in the coverage gap.  Both bills contain physician payment “sunshine” provisions, though the reporting requirements under the House bill are more extensive.  The major differences in regard to payments extracted from manufacturers are that the House bill would require drug manufacturer rebates for dual eligibles, while the SFC Chairman’s Mark would not.  On the other hand, the Mark would impose aggregate annual “sector” fees of $2.3 billion and $4 billion on the drug and device industries, respectively, to fund Medicare, while the House bill does not contain such fees.

You will find a summary of the drug- and device-related provisions of the SFC Chairman’s Mark here.  Please note that this summary only addresses provisions of the Mark that would most directly affect drug and device manufacturers.  There are many other aspects of this bill that would have an indirect but considerable impact on drug and device manufacturers.

The health care reform debate in Congress is fluid.  The Senate Finance Committee bill could change substantially in mark-up, or it might not be reported out of Committee at all.  The House Energy and Commerce Committee bill faces similar uncertainty as it goes to a potential second mark-up and to the House floor.  We will be following these developments closely and reporting on the aspects that most directly affect drug and device manufacturers.

By Kurt R. Karst –      

On September 15, 2009, FDA issued its long-awaited decision responding to several citizen petitions submitted in 2005 and 2006 (available here, here, here, and here) concerning the approval of ANDAs for generic versions of Wyeth Pharmaceuticals’ ZOSYN (piperacillin sodium; tazobactam sodium) Injection.  FDA’s decision to grant the petitions (and largely deny a Wyeth petition) and approve ANDAs reaffirms an Agency policy that FDA will, in the context of discontinued drug product formulations, waive its so-called “exception excipient regulations” to permit the receipt and approval of an ANDA for a drug product containing a so-called “non-exception excipient” change from the Reference Listed Drug (“RLD”).
 
FDC Act § 505(j)(4)(H) states that FDA must approve an ANDA unless, among other things:

information submitted in the application or any other information available to [FDA] shows that (i) the inactive ingredients of the drug are unsafe for use under the conditions prescribed, recommended, or suggested in the labeling proposed for the drug, or (ii) the composition of the drug is unsafe under such conditions because of the type or quantity of inactive ingredients included or the manner in which the inactive ingredients are included.

FDA’s regulations implementing FDC Act § 505(j)(4)(H), generally, are found in the Agency’s ANDA content and format regulations at 21 C.F.R. 314.94.  Pertinent regulations on inactive ingredient changes for certain types of generic drug products are set forth in 21 C.F.R. § 314.94(a)(9).  FDA’s regulations for parenteral drug products at 21 C.F.R. § 314.94(a)(9)(iii) state:

Generally, a drug product intended for parenteral use shall contain the same inactive ingredients and in the same concentration as the [RLD] identified by the applicant under paragraph (a)(3) of this section.  However, an applicant may seek approval of a drug product that differs from the reference listed drug in preservative, buffer, or antioxidant provided that the applicant identifies and characterizes the differences and provides information demonstrating that the differences do not affect the safety or efficacy of the proposed drug product.

Preservative, buffer, and antioxidant changes in generic parenteral drug products are referred to as “exception excipients,” which may qualitatively or quantatively differ from the RLD formulation.  Other regulations at § 314.94(a)(9)(iv) identify exception excipients for generic ophthalmic and otic drug products (i.e., preservative, buffer, substance to adjust tonicity, and thickening agent).  Excipients not identified in these regulations are referred to as “non-exception excipients.”  These regulations find their parallel in 21 C.F.R. § 314.127(a)(8)(ii), which addresses the grounds for an FDA refusal to approve an ANDA for a parenteral, ophthalmic, or otic drug product.  For example, 21 C.F.R. § 314.127(a)(8)(ii)(B) states: “FDA will consider an inactive ingredient in, or the composition of, a drug product intended for parenteral use to be unsafe and will refuse to approve the [ANDA] unless it contains the same inactive ingredients, other than preservatives, buffers, and antioxidants, in the same concentration as the listed drug. . . .”

Notwithstanding FDA’s exception excipient regulations, the Agency has, on occasion, but only in very limited circumstances, waived its exception excipient regulations to permit the receipt and approval of an ANDA for a drug product containing a non-exception excipient change from the RLD.  Specifically, FDA has granted waivers under 21 C.F.R. § 314.99(b), which states that a generic applicant “may ask FDA to waive . . . any requirement that applies to the applicant under §§ 314.92 through 314.99.”  FDA can grant such a waiver if the Agency finds: “(1) the applicant’s compliance with the requirement is unnecessary for the agency to evaluate the application or compliance cannot be achieved; (2) the applicant’s alternative submission satisfies the requirement; or (3) the applicant’s submission otherwise justifies a waiver.”  21 C.F.R. § 314.90(b).

FDA has historically granted § 314.99(b) waivers when an ANDA applicant seeks approval to market a drug product containing a non-exception excipient used in a discontinued RLD formulation that is not used in the currently-marketed RLD formulation.  For example, in 2005, FDA granted a petition permitting generic applicants seeking approval to market generic SANDOSTATIN (octreotide acetate) Injection to substitute a different tonicity agent (a non-exception excipient change) and buffer system because “the inactive ingredients (including the buffer system and tonicity agent) used in the discontinued formulation of Sandostatin do not make that formulation unsafe. . . [and because] the discontinued formulation of Sandostatin is no less safe and effective than the new formulation.” 

FDA’s ZOSYN petition decision is in the same vein as the SANDOSTATIN petition response.  In September 2005, FDA approved an NDA supplement for a new formulation of ZOSYN containing edetate disodium dihydrate (“EDTA”) and citric acid monohydrate, which reportedly function in the drug product as a chelator (a non-exception excipient) and a buffer, respectively.  Several petitions were submitted to FDA requesting that the Agency: (1) determine that the formulation of ZOSYN originally approved by FDA was not discontinued for safety or efficacy reasons; and (2) accept ANDAs for generic versions of ZOSYN duplicating the discontinued formulations (i.e., without EDTA and citric acid).  In granting these petitions, FDA stated:

The Agency may rely on § 314.99(b) (21 CFR 314.99(b)) to grant a waiver of the regulation requirement – that the ANDA and NDA formulations contain the same inactive ingredients in the same concentrations as the RLD, with limited exceptions for preservatives, buffers, and antioxidants – insofar as the statutory requirement regarding safety of inactive ingredients has been met. . . .  FDA may approve ANDAs for piperacilin and tazobactam for injection duplicating the original Zosyn formulation.  Such ANDAs would differ from the reformulated Zosyn with respect to the inactive ingredient EDTA, which is not a preservative, buffer, or antioxidant.  Here, experience with Wyeth's original Zosyn formulation and FDA’s recent analysis has shown that the inactive ingredients in the ANDA for piperacilin and tazobaetam for injection duplicating the original Zosyn formulation are safe. . . .  Because the original Zosyn formulation clearly meets the statutory safety standard with respect to inactive ingredients, the Agency may rely on § 314.99(b) to grant a waiver of the regulation requirement that the ANDA formulation contain the same inactive ingredients in the same concentration with the limited exceptions for preservatives, buffers, and antioxidants.

It is also noteworthy that ZOSYN contains an old antibiotic drug and is subject to § 4 of the “QI Program Supplemental Funding Act of 2008” (the “QI Act”).  The QI Act was enacted on October 8, 2008 and amended the FDC Act to add new § 505(v) – “Antibiotic Drugs Submitted Before November 21, 1997” – to create Hatch-Waxman benefits for old antibiotics.  Under a transition provision included in the QI Act, NDA holders and patent owners can list patents in the Orange Book, and generic applicants can qualify for 180-day exclusivity.  Shortly after the enactment of the QI Act, a patent was listed in the Orange Book covering ZOSYN.  Those generic applicants who timely amended their pending ANDAs for generic ZOSYN to include a Paragraph IV Certification to that patent are eligible for shared 180-day exclusivity.

By Ricardo Carvajal –

FDA has issued a letter to the tobacco industry offering a reminder that, under the standard for cigarettes in FDCA section 907(a)(1)(A), a cigarette or any of its component parts may not contain “an artificial or natural flavor (other than tobacco or menthol) or an herb or spice, including strawberry, grape, orange, clove, cinnamon, pineapple, vanilla, coconut, licorice, cocoa, chocolate, cherry, or coffee, that is a characterizing flavor of the tobacco product or tobacco smoke.”  That prohibition on "characterizing flavors" takes effect on September 22, 2009, and any cigarette that violates the prohibition is adulterated and subject to seizure.  FDA has not explained what makes a flavor a "characterizing flavor."  However, those responsible for the violation may be subject to injunction, civil penalties, and criminal prosecution.  The letter states that FDA “intends to use the full range of enforcement tools within the Agency’s authority to ensure compliance with the new requirement.”

The standard for cigarettes applies to any tobacco product that meets the following definition:

(3) CIGARETTE.—The term “cigarette”—
(A) means a product that—
(i) is a tobacco product; and
(ii) meets the definition of the term “cigarette” in section 3(1) of the Federal Cigarette Labeling and Advertising Act [("FCLAA")]; and

(B) includes tobacco, in any form, that is functional in the product, which, because of its appearance, the type of tobacco used in the filler, or its packaging and labeling, is likely to be offered to, or purchased by, consumers as a cigarette or as roll-your-own tobacco.

Section 3(1) of the FCLAA defines a cigarette as “(A) any roll of tobacco wrapped in paper or in any substance not containing tobacco, and (B) any roll of tobacco wrapped in any substance containing tobacco which, because of its appearance, the type of tobacco used in the filler, or its packaging and labeling, is likely to be offered to, or purchased by, consumers as a cigarette described in subparagraph (A).”

The letter states that FDA will consider products that meet these criteria to be cigarettes, “even if they are not labeled as ‘cigarettes’ or are labeled as cigars or as some other product.”  This would seem to indicate that some manufacturers that have been reported to be revamping their flavored cigarette offerings to try to work around the prohibition may be in FDA's crosshairs.

By Kurt R. Karst –
 
At a September 10, 2009 Senate Judiciary Committee Executive Business Meeting, Senator Herb Kohl (D-WI) stated his plans to pursue a substitute amendment to S. 369, the Preserve Access to Affordable Generics Act, that would make significant changes to the proposed legislation.  (A webcast of the Executive Business Meeting is available here.  See minutes 46-49 for Sen. Kohl’s remarks.) 

Under the version of S. 369 Sen. Kohl introduced in February 2009, it would be unlawful for a person, in connection with the sale of a drug product, to be a party to any agreement resolving or settling a patent infringement claim in which a generic applicant receives anything of value, and for a generic applicant to agree not to research, develop, manufacture, market, or sell the generic product for any period.  Sen. Kohl’s substitute amendment would largely reverse course, permitting reverse payments between brand and generic companies if such companies can prove that the deals are “pro-competitive.”  The Federal Trade Commission (“FTC”) would reportedly have to challenge the deals and the burden would be on the companies to prove in court that the agreements are pro-competitive; however, it is unclear what evidence would be needed to prove pro-competitiveness.   In addition, we understand that Sen. Kohl’s substitute amendment would allow the FTC to levy fines of up to three times the revenue of the brand name drug in question if the agreement is found to be unlawful. 

Although the Senate Judiciary Committee was originally scheduled to vote on Sen. Kohl’s substitute amendment at the September 10th Executive Business Meeting, we understand that some Committee members requested an additional week to study the amendment, and that Sen. Orrin Hatch (R-UT) has written a letter to Sen. Kohl expressing his concerns about the proposal.  The Committee is scheduled to further consider – and likely vote on – the measure at its September 17th Executive Business Meeting.

If Sen. Kohl’s substitute amendment is passed, it will be at odds with the reverse payment provision added to the House Energy and Commerce Committee’s version of H.R. 3200, the America’s Affordable Health Choices Act, earlier this summer.  As we previously reported, in late July, the Committee passed by voice vote an amendment to H.R. 3200 sponsored by Rep. Bobby Rush (D-IL) that would prohibit reverse payment settlements between generic and brand-name drug companies.

By Ricardo Carvajal –

USDA’s Food Safety and Inspection Service (“FSIS”) has released a prepublication version of an Advanced Notice of Proposed Rulemaking (“ANPRM”) that seeks additional public input on the conditions under which FSIS should permit use of the claim “natural” in the labeling of meat and poultry products (FSIS has authority to review and approve labeling prior to marketing of such products).  FSIS previously signaled its intent to issue a proposed rule.  However, in response to a prior Federal Register notice and a public hearing that addressed the use of “natural” in labeling, USDA received over 12,000 comments that expressed a wide range of views.  In addition, FSIS  received several petitions requesting that FSIS adopt particular interpretations of “natural.”  The evident lack of any consensus on the meaning of “natural” has prompted FSIS to seek another round of comment.

In its ANPRM, FSIS asks for comment on numerous issues, including: whether FSIS should establish a definition of “natural” by regulation or maintain a more flexible definition by policy;  whether multi-functional ingredients (e.g., ingredients that may have both flavoring and antimicrobial effects) can properly be labeled as “natural;” whether the use of recently developed processing methods should be permitted for “natural” products; whether “enhancement” (i.e., addition of marinades/flavoring/tenderizing solutions) should be permitted in “natural” products; whether conditions under which animals are raised should be considered (the Agricultural Marketing Service currently permits use of the claim “naturally raised”); and whether there should be a single Federal definition of “natural” (currently FSIS and FDA maintain separate policies).  In addition, FSIS makes clear that it continues to consider the use of carbon monoxide in modified atmosphere packaging systems to be incompatible with a “natural” claim, and requests comment on that issue.

By Cassandra A. Soltis –

Regrow your hair.  Cure cancer.  Obtain a photographic memory.  These are just some of the claims that Kevin Trudeau, infomercial marketer extraordinaire, has made for various products over the years.  The Federal Trade Commission (“FTC”) is all-too-familiar with Mr. Trudeau and his promotional tactics: since 1998, Trudeau has entered into several Orders with the Agency that collectively made him: promise he would not misrepresent the benefits of any product without competent and reliable evidence; submit infomercials to the FTC before they are televised; and stop marketing Coral Calcium as a cure for cancer or from advertising any products in infomercials, except to promote his publications, provided he did not refer to any other product he was marketing.     

His troubles with the FTC resurfaced in 2007, when he began promoting his book The Weight Loss Cure “They” Don’t Want You To Know About.  The FTC brought civil contempt proceedings against Mr. Trudeau, arguing that he had violated a 2004 Consent Order’s command that he not misrepresent the content of his book.  FTC v. Trudeau, No. 08-4249, 2009 U.S. App. LEXIS 19318, at *11 (7th Cir. Aug. 27, 2009).  Trudeau countered that he was merely quoting what he wrote in the book.  However, the district court disagreed, finding that Trudeau could not cherry-pick certain phrases which “did not accurately portray the book’s overall content.”  Id. at *12.  The court found Trudeau in contempt of court, required that he pay $37.6 million, and banned him for three years from appearing in infomercials.  

Trudeau appealed to the court of appeals.  On August 27, 2009, the United States Court of Appeals for the 7th Circuit agreed with the district court’s contempt finding, stating that Trudeau “clearly misrepresented [his] book’s content.”  Id. at *3.

However, the Court of Appeals rejected the district court’s monetary sanction because the district court’s order did not indicate “how the court arrived at the figure it did, whether the award will be used to reimburse consumers, and what happens if there’s money left over after all reimbursements are paid.”  Id. at *38. 

In addition, the Court ruled that the district court had erred in the manner in which it had imposed sanctions.  It found that although the case was labeled as civil contempt, the district court had actually imposed a remedy that appeared to be a criminal contempt sanction, without providing certain constitutional safeguards that apply in criminal cases. 

The Court also found the infomercial ban to be improper because the ban was to last for three years, regardless of what Trudeau did in the future.  Id. at *63-65.   

If history is any indication, the courts have not seen the last of Kevin Trudeau.

FDA Law Blog and Hyman, Phelps & McNamara, P.C. wish to congratulate Olsson Frank Weeda Terman Bode Matz PC on celebrating their 30th Anniversary as a food and drug law firm.  Let us say, you’ve aged extremely well!  We wish you much success over the next 30 years.

By Kurt R. Karst –      

Since the enactment of the Medicare Prescription Drug, Improvement, and Modernization Act of 2003 (“MMA”), Hatch-Waxman scholars have wondered how FDA might answer the following question: “What is the effect of a forfeiture of 180-day exclusivity eligibility due to the failure of a first applicant to obtain tentative ANDA approval pursuant to FDC Act § 505(j)(5)(D)(i)(IV) when at least one other first applicant remains eligible for 180-day exclusivity?”  FDA’s September 9, 2009 approval of ANDAs for generic versions of STARLIX (nateglinide) Tablets provides the answer to that question. 

FDC Act § 505(j)(5)(D)(i)(IV), as added by the MMA, states the 180-day exclusivity eligibility is forfeited if “[t]he first applicant fails to obtain tentative approval of the application within 30 months after the date on which the application is filed, unless the failure is caused by a change in or a review of the requirements for approval of the application imposed after the date on which the application is filed” (emphasis added).  The term “first applicant” is defined at FDC Act § 505(j)(5)(B)(iv)(II)(bb) to mean “an applicant that, on the first day on which a substantially complete application containing a [Paragraph IV Certification] is submitted for approval of a drug, submits a substantially complete application that contains and lawfully maintains a [Paragraph IV Certification] for the drug.”  These and other provisions of FDC Act § 505(j), as amended by the MMA, concerning the scope and effect of 180-day exclusivity effectively create three categories of ANDA applicants relevant to a forfeiture under FDC Act § 505(j)(5)(D)(i)(IV):

(1)  “Eligible first applicants” (i.e., those first applicants who have not forfeited 180-day exclusivity eligibility under FDC Act § 505(j)(5)(D)(i));

(2)  “Ineligible first applicants” (i.e., those first applicants who have forfeited 180-day exclusivity eligibility under FDC Act § 505(j)(5)(D)(i)(IV), but nevertheless remain first applicants because their ANDAs continue to “lawfully maintain” a Paragraph IV Certification); and

(3)  “Subsequent applicants” (i.e., those applicants whose ANDAs contain a Paragraph IV Certification but who are not first applicants, and therefore are subject to an eligible first applicant’s 180-day exclusivity).

In the case of generic STARLIX, we understand that there were multiple first applicants, but that FDA determined that some (but not all) first applicants forfeited 180-day exclusivity eligibility under FDC Act § 505(j)(5)(D)(i)(IV).  This scenario necessarily led FDA to consider several questions, including:

(1) Can an ineligible first applicant obtain approval for its ANDA before commencement and/or expiration of a 180-day exclusivity period triggered by commercial marketing by an eligible first applicant?; and  

(2) If an ineligible first applicant obtains approval and begins marketing of the drug, does that marketing start the 180-day exclusivity period for all eligible first applicants?

FDA’s decision to approve ANDAs for first applicants who forfeited 180-day exclusivity eligibility under FDC Act § 505(j)(5)(D)(i)(IV) by failing to obtain timely tentative ANDA approval affirmatively answers the first question.  And as a result of FDA recognizing that an ineligible first applicant that “lawfully maintains” a Paragraph IV Certification to an Orange Book-listed patent is nevertheless a first applicant, and by operation of FDC Act § 505(j)(5)(B)(iv)(I), which states, in relevant part, that “the first commercial marketing of the drug . . . by any first applicant” (emphasis added) triggers 180-day exclusivity, FDA also answered the second question in the affirmative.

Although FDA has in the past published letters explaining the Agency’s post-MMA 180-day exclusivity decisions, FDA has not yet done so in this case.  FDA could, as the Agency has done in other cases concerning 180-day exclusivity forfeiture under FDC Act § 505(j)(5)(D)(i)(IV), let its approval decisions stand as its explanation and policy. 

UPDATE:

• On September 11, 2009, FDA issued a Letter Decision concerning its determination of 180-day exclusivity for Nateglinide Tablets.

On September 10, 2009, Hyman, Phelps & McNamara’s John R. Fleder and William T. Koustas will speak at a Thompson Interactive audioconference on FDA’s use of criminal search warrants.  The audioconference, titled “Unannounced FDA Raids: Be Ready Before They Appear at Your Door,” will cover the following issues:

• When will the FDA use a search warrant rather than a Form 482?  Can an investigator enter your facility if she doesn’t have a 482 or a search warrant?
• The administrative inspection warrant vs. a criminal search warrant – does one have more power than the other?  How should you prepare for each?
• Can you prevent an investigator from entering, or block them from access to areas not covered by a warrant?  Can you ask for outside counsel to be present without obstructing justice?
• What can you ask investigators?  How should you respond to their questions?  Can you follow them throughout the search?
• How should you manage agent access to other employees?
• Where should documents be filed and stored before a raid to prevent agents from viewing privileged information they don’t have a legal right to see?
• Expect the unexpected – preparing for and managing other raid issues like media attention and employee fears.

Additional information on the audioconference, including registration information, is available here.

For the past couple of years the American Bar Association (“ABA”) has published a list of the top 100 legal “blawgs” in the blogosphere – The ABA Blawg 100!  The ABA is currently soliciting nominations for its 3rd annual list.  Although FDA Law Blog was left off the 2nd annual list, we are determined to make the cut this year.  But we need the help of our loyal blog readers to do that.  There is a lot of competition out there for this coveted honor.  So, please please visit the ABA’s “Blawg 100 Amici” website and nominate FDA Law Blog!  Thank you!  (It will only take a couple of minutes.)

By Ricardo Carvajal –

FDA previously announced that the Reportable Food Registry that the agency is required to establish by section 417 of the Federal Food, Drug, and Cosmetic Act ("FD&C Act") would become operational on September 8, 2009, and that responsible parties would be expected to comply with the reporting obligations imposed under section 417 on that date.  However, the agency has just updated its guidance document on the Registry to make clear that, while responsible parties must comply with their reporting obligations as of September 8, “FDA intends to consider exercising enforcement discretion for a period of 90 days, until December 8, 2009, in circumstances where FDA determines that a responsible party has made a reasonable effort to comply with the requirements of section 417 of the FD&C Act and has otherwise acted to protect public health.”  This is a welcome announcement, given the relative complexity of the reporting obligations under section 417, and the many questions that have already arisen about FDA's implementation of the Registry.

The Food and Drug Law Institute is sponsoring a webinar on the Registry on September 10.  For registration and other information, see here.

By Michelle L. Butler –

On September 1, 2009, the Health Resources and Services Administration (“HRSA”) issued a Final Notice regarding qualified children’s hospitals and the 340B Drug Pricing Program.  See 74 Fed. Reg. 45,206 (Sept. 1, 2009).  Section 340B of the Public Health Service Act (“PHS Act”) lists the types of entities (i.e., Covered Entities) to which manufacturers of covered outpatient drugs are required to extend 340B Ceiling Prices.  See 42 U.S.C. § 256b(a)(4).  Children’s hospitals are not on this list.  Section 6004 of the Deficit Reduction Act of 2005 (the “DRA”) amended the statutory provisions related to the Medicaid Drug Rebate Program to include certain qualified children’s hospitals as Covered Entities for purposes of the Medicaid Drug Rebate Program.  See 42 U.S.C. § 1396r-8(a)(5)(B).  There was no similar change to section 340B of the PHS Act to include children’s hospitals on that list of Covered Entities.  In July 2007, HRSA published in the Federal Register proposed guidelines for children’s hospitals and requested comments on those proposed guidelines.  In the September 1, 2009 Federal Register Notice, HRSA addresses the comments and issues its guidance.

HRSA has determined that despite the fact that qualified children’s hospitals were not listed in the section 340B list of Covered Entities, such hospitals are Covered Entities by virtue of their inclusion in the definition of Covered Entities in the Medicaid Drug Rebate statute.  74 Fed. Reg. at 45,206-07, 45,209.  Accordingly, manufacturers are required to extend 340B Pricing to children’s hospitals that the meet the statutory qualifications.  HRSA has also determined that the terms of the Pharmaceutical Pricing Agreements between manufacturers and the Secretary of the Department of Health and Human Services are broad enough to include qualified children’s hospitals.

The final guidelines describe the process for admission of children’s hospitals into the 340B Drug Pricing Program.  74 Fed. Reg. at 45,209-11.  Prior to entry into the 340B Drug Pricing Program, a children’s hospital will need to provide certifications of compliance with a number of requirements, including the requirement that it will not participate in a group purchasing organization as of the effective date of its entry into the program.  Once a qualified children’s hospital has satisfied the enrollment criteria, HRSA, acting through the Office of Pharmaceutical Affairs (“OPA”), will list any such qualified children’s hospitals on the 340B Drug Pricing Program Database in its standard quarterly updates. 

The final guidelines also state that section 6004 of the DRA authorized entry of qualified children’s hospitals into the 340B Drug Pricing Program as of the effective date of the DRA, which was February 8, 2006.  According to the guidelines, therefore, qualified children’s hospitals are eligible for 340B Drug Pricing back to February 8, 2006, once they are admitted to the 340B Program and listed on the 340B Drug Pricing Program Database.  However, a children’s hospital will be eligible for retroactive discounts only to the extent that it has satisfied all requirements for participation in the 340B Drug Pricing Program back to the date discounts are requested.  The guidelines specify that children’s hospitals may request retroactive discounts directly from pharmaceutical manufacturers when the following requirements are satisfied:

1. The children’s hospital is listed on the 340B Covered Entity Database as eligible to purchase under 340B within one year of publication of this notice;
2. The children’s hospital sent a request in writing to each manufacturer of the drug(s) for which retroactive discounts are sought within 30 days of the children’s hospital having been listed as eligible to purchase under 340B on the Covered Entity Database;
3. The covered outpatient drugs must have been purchased on or after February 8, 2006;
4. The covered outpatient drugs must not have generated Medicaid rebates (the children’s hospital must have appropriate documentation to demonstrate this);
5. The covered outpatient drugs must not have been sold or transferred to a person who was not a patient of the children’s hospital; and
6. The covered outpatient drugs must have been purchased on or after the date on which the children’s hospital satisfied all requirements for participation in the 340B Program as outlined in [the guidance].

74 Fed. Reg. at 45,211.