On November 3, 2011, the U.S. Court of Appeals for the Tenth Circuit affirmed the findings of the District of Wyoming, granting the dismissal of the lawsuit filed by Cody Laboratories, Inc. (Cody) and Lannett Co., Inc. (Lannett) and finding in favor of the U.S. Food and Drug Administration (FDA). Finding that the companies had failed to exhaust administrative remedies, the Tenth Circuit found that it was without jurisdiction to decide the merits of the companies’ claims. The Tenth Circuit decision may be accessed here.

The lawsuit ultimately arose from two FDA Warning Letters that were issued to Cody and Lannett in 2009. Found here and here, the Warning Letters contain directives from the FDA to cease all manufacturing of unapproved morphine sulfate products, finding that they did not constitute grandfathered drugs under the Federal Food, Drug and Cosmetic Act (FDCA). Grandfathered drugs are those that entered the market prior to the enactment of the FDCA in 1938 and its 1962 amendments and are exempted from the requirement to show effectiveness. Finding that the products were not grandfathered drugs, the FDA concluded that the products were new drugs under the FDCA, thus requiring NDAs. In response to the companies’ challenge to the lawfulness of the warning letters, the District Court for the District of Wyoming found that because warning letters did not constitute final agency action, it lacked the jurisdiction to entertain the suit.

On appeal, the Tenth Circuit held that the companies’ claims were not reviewable because the companies had failed to exhaust their available administrative remedies. In particular, the Tenth Circuit found that the failure to utilize the citizen petition procedure provided by the FDA rendered the companies’ claims unreviewable. 21 C.F.R. § 10.30 provides a citizen petition procedure which affords interested parties the opportunity to receive FDA review of an otherwise unfavorable Agency decision or action. Because Cody and Lannett failed to complete this internal agency review in connection with the decision that the products constituted new drugs under the FDCA, the Tenth Circuit affirmed the district court’s decision that it was without jurisdiction to consider the merits of the companies’ claims.

Warning letters are generally the Agency’s first course of action upon discovery of a violation of the FDCA and/or FDA regulations. These letters provide formal notification to offending parties of the specific violations that FDA has observed and gives them the opportunity to respond. If after receiving a FDA Warning Letter the offending party takes all necessary measures to correct such violations, the FDA will typically take no further action. However, because these letters and the suggested corrective measures therein do not technically bind named parties to a specific course of action, courts have found that FDA Warning Letters do not constitute final agency action for the purpose of judicial review. This is so even though it is the practice of FDA to post all warning letters onto its website and thereby subject the offending party to public criticism.

A citizen petition is initiated by an interested party and seeks some form of relief from FDA action. In holding that the companies did not exhaust their administrative remedies because they failed to file citizen petitions, the court appears to have overestimated the efficacy of this process. For instance, citizen petitions are often thought to be an ineffective means for challenging FDA action because FDA’s regulations allow for the FDA to indefinitely delay decision-making with little recourse for the interested party. In particular, 21 C.F.R. § 10.30(e)(2) provides that the FDA may respond within 180 days by either approving, denying, or withholding a final decision of a citizen petition. Where a final decision is withheld upon conclusion of the 180 day time period, the FDA’s reasoning may be that it has not had the opportunity to render a decision because of other Agency priorities, thus prolonging the timeframe for obtaining final agency action. Thus, because the FDA is not forced to provide a final decision within a definitive timeframe, citizen petitions are often viewed as a woefully ineffective means of obtaining relief.

For more information concerning the FDCA or FDA regulations, please contact us at contact@fuerstlaw.com.

On November 9, 2011, the U.S. Food and Drug Administration (FDA) published “SOP: Decision Authority for Additional or Changed Data Needs for Premarket Submissions.” The document sets forth limitations to the data requirements that agency reviewers may request when reviewing various types of premarket submissions for medical devices. Found here, the document details how reviewers will be limited in the information they request by requiring management’s approval, or “concurrence,” in order to seek new or additional data from those seeking agency review.

Prior to the SOP, there was no written policy in place serving to limit reviewers’ data requests. Thus, device sponsors often found data requests onerous and irrelevant to the safety and efficacy of medical devices. Hopefully, limitations to such data requests will benefit device sponsors by increasing the predictability and efficiency of the premarket review process.

For more information regarding the FDA premarket review process, contact us at contact@fuerstlaw.com.

On November 18, 2011, the U.S. Food and Drug Administration (FDA) announced its decision to revoke the approval of the breast cancer indication for Avastin. Because Avastin will still be approved for its other uses, including the treatment of brain, kidney, lung and colon cancer, the drug will remain on the market despite this recent decision. The FDA initially approved Avastin for the treatment of breast cancer based on evidence showing that the drug may restrict tumor growth. However, according to the FDA’s decision to revoke its approval, further clinical data has shown that the drug may only marginally limit tumor growth.

Found here, the decision of FDA Commissioner Margaret Hamburg details the procedures whereby Avastin gained approval for this indication and the reasoning for its recent revocation. In 2008, FDA’s Center for Drug Evaluation and Research (CDER) approved Avastin for the treatment of breast cancer through the Agency’s accelerated approval process. Set forth in 21 C.F.R. § 601.40-46, this process allows biological products to secure approval for the treatment of life-threatening diseases upon showing some evidence that the drug may provide clinical benefit. However, as a condition to accelerated approval, manufacturers are required to continue clinical testing and report their findings to the FDA. Under 21 C.F.R. § 601.43(a), the FDA may withdraw approval where the required postmarketing testing “fails to verify clinical benefit,” where applicants are noncompliant in performing such testing, and where applicants otherwise fail to comply with other postmarketing restrictions.

Because FDA determined that further studies did not verify the level of clinical benefit that prompted the original approval, CDER proposed its withdrawal of approval for this indication in December 2010. Thereafter Avastin’s sponsor, Genentech, Inc., was afforded an opportunity to show the FDA why this approval should not be withdrawn. This opportunity for hearing is mandated by 21 C.F.R. § 601.43(b). Genentech’s arguments were unavailing, and the FDA ultimately withdrew its approval for the breast cancer indication.

While this indication is no longer permitted in product labeling, doctors may still prescribe the drug for use in the treatment of breast cancer. Although manufacturers are limited to marketing drugs for the indications approved in product labeling, FDA regulations do not prevent doctors from prescribing drugs for other uses, a practice known as “off-label” use. Thus, despite the revocation of this indication in product labeling, Avastin may continue to be used to treat breast cancer.

For more information regarding the FDA’s drug approval process, please contact us at contact@fuerstlaw.com.

On November 10, 2011, the U.S. Food and Drug Administration (FDA) announced its approval of the first blood product derived from cord blood indicated for treatment as a stem cell therapy. HEMACORD, the hematopoietic progenitor cell-cord (HPC-C) blood product, is intended for use in HPC transplant procedures for individuals affected with various blood disorders.

FDA has recently begun requiring HPC-C manufacturers to submit license applications or investigational new drug applications in order to market these products. Having issued a guidance document detailing the regulatory requirements in 2009, FDA instituted a two-year phase-in period for HPC-C manufacturers. According to the FDA’s press release detailing the approval, found here, HEMACORD marks the first approval of a license application for cord blood as the Agency’s two-year phase-in period for HPC-C manufacturers comes to a close. The phase-in period ended on October 20, 2011.  While the regulatory environment surrounding HPCs and stem cells in general has proven cumbersome to manufacturers, with approvals being scarce since the regulations were promulgated in 2001, the approval may be the first of many in the coming years.

We question, however, whether this “product” approval will ultimately benefit anyone. Doctors have been treating their patients using cord blood for more than 20 years, and more than 20,000 patients have been successfully treated in that time. More information about the history of cord blood transplantation may be found here.

For more information about the FDA regulations or the FDA approval process, contact us at contact@fuerstlaw.com.

On November 4, 2011, a Bill was introduced before the U.S. House of Representatives that proposes to restrict the definition of “new dietary ingredient” (NDI) under the Federal Food, Drug and Cosmetic Act (FDCA). Introduced by Representative Dan Burton, the “Dietary Supplement Protection Act of 2011” seeks to alter the current definition of NDI by changing the applicable dates for which a dietary ingredient must have previously been marketed in the United States.

Currently, a NDI is defined under the FDCA as “a dietary ingredient that was not marketed in the United States before October 15, 1994 and does not include any dietary ingredient which was marketed in the United States before October 15, 1994.” 21 U.S.C. § 350(b). Those dietary ingredients that are not considered NDIs are commonly referred to as “grandfathered” ingredients. Under the FDCA, only grandfathered ingredients are “generally recognized as safe” (GRAS) for human consumption and may be used as ingredients in dietary supplements without prior FDA notification. On the other hand, if an ingredient is considered a NDI, manufacturers must notify the FDA prior to marketing any product containing such an ingredient. Under 21 C.F.R. § 190.6, manufacturers of dietary supplements containing NDIs must submit a premarket notification, demonstrating that these ingredients are safe for human consumption, at least 75 days before marketing their products.

Found here, the Bill proposes to amend the FDCA “by striking ‘October 15, 1994’ each place it appears and inserting ‘January 1, 2007’.” According to the Bill, Congress believes that the definition of grandfathered ingredients is too narrow based on current knowledge on a range of dietary ingredients and their safety for human consumption. Thus, the Bill will limit the definition of NDI, while at the same time expanding the scope of ingredients that are considered grandfathered under the Act.

For more information about the FDCA or FDA regulations, please contact us at contact@fuerstlaw.com.

On November 18, 2011, the World Trade Organization (WTO) published its report on the ongoing Country of Origin Labeling (COOL) dispute. Implemented in 2008 as part of the Farm Bill, U.S. manufacturers began requiring country-of-origin to be designated in labeling of meats and other goods regulated by the U.S. Department of Agriculture (USDA). Found here, the WTO report details the complaints raised by Canada and Mexico, including the contention that the labeling requirements constitute Technical Barriers to Trade (TBT), in violation of international treaties between the countries.

Ultimately, the WTO’s decision was mixed. While the COOL requirements were generally found to pose technical barriers to trade by discouraging imports from Canada and Mexico, the U.S. did not lose out completely. Rather, WTO decided that although the COOL requirements must stop generally, there are certain exceptions to its findings, including meat. Thus, country of origin labeling will continue to be declared on meat products in the United States without further issue from Canada or Mexico. In addition, because the decisions of the WTO are not technically binding, it is possible for the COOL program to continue in the United States with only informal action, such as tariffs, etc., available as recourse.

For more information about USDA labeling requirements, contact us at contact@fuerstlaw.com.

On November 11, 2011, the U.S. Food and Drug Administration (FDA) appealed a recent decision issued by the District Court for the Middle District of Florida, finding that the FDA lacked the authority to prohibit state-licensed veterinary compounding. The September 12, 2011 decision being appealed details the longstanding practice of pharmacy compounding in the context of veterinary medicine.

Compounding is commonly defined by state law as the practice of filling prescriptions through individualized preparation, as opposed to the manufacturing of drugs in bulk. Unlike the compounding of human drugs, over which the FDA acknowledges it lacks full regulatory control if the compounding pharmacy meets certain requirements, the FDA maintains that it possesses the authority to regulate veterinary compounding.

The case originated after the accidental death of 21 polo horses that received compounded drugs from Franck’s Lab, Inc. (Franck’s), an incident that was ultimately linked to a mathematical error in the issuing veterinarian’s prescription. In addition, Franck’s had received FDA Warning Letters in 2004 and 2005, alleging that Franck’s was impermissibly manufacturing drugs in violation of the Federal Food, Drug and Cosmetic Act (FDCA). In response to the Warning Letters, Franck’s argued that “[s]tate law and good compounding practices . . . allow bulk compounding as long as there is a valid patient physician (veterinarian) relationship.” Because the FDA permits compounding of drugs for human use, Franck’s argued that the FDA must allow the same for veterinary compounding. The FDA, however, rejected this argument and brought suit against Franck’s in April 2010 seeking injunctive relief to stop Franck’s from compounding and distributing animal drugs.

In its order, the District Court found for Franck’s and held that because the states have traditionally exercised authority over pharmacy compounding, the states likewise have the authority to regulate the compounding of animal drugs. By filing its notice of appeal, the FDA has signaled that it is not willing to concede the issue of its authority to regulate veterinary compounding.

Fuerst Ittleman will continue to monitor the Franck’s case. For more information, please contact us at contact@fuerstlaw.com.

On November 7, 2011, Judge Richard Leon of the United States District Court for the District of Columbia granted a preliminary injunction on behalf of five tobacco companies challenging the implementation of the FDA’s new graphic cigarette warning labels. As a result of the injunction, the FDA’s new cigarette labeling requirements, which were scheduled to take effect in September 2012, are now blocked from taking effect until fifteen months after resolution of the plaintiffs’ claims on the merits. A copy of the Court’s opinion can be read here.

As we previously reported, on June 21, 2011, pursuant to the authority granted to it by the Family Smoking Prevention and Tobacco Control Act to regulate tobacco, the FDA released nine new graphic warning labels that were required to appear on every pack of cigarettes sold in the US and in every cigarette advertisement starting no later than September 2012. In response to the FDA’s new rule, five tobacco companies (R.J. Reynolds Tobacco Company, Lorillard Tobacco Company, Commonwealth Brands, Inc., Liggett Group LLC, and Santa Fe Natural Tobacco Company, Inc.) filed a complaint in the United States District Court for the District of Columbia alleging that the FDA’s new cigarette labeling rules violated the First Amendment and the Administrative Procedure Act.

The five companies also sought an injunction to prohibit the rules from going into effect until fifteen months after a final decision has been rendered on the merits of their case. More background information involving this case can be read in our prior report here. In order for a court to grant a preliminary injunction, it must determine the following: 1) whether there is a substantial likelihood of success on the merits for the moving party; 2) whether the movant will suffer irreparable harm if the injunction is not granted; 3) whether the injunction will substantially injure other interested parties; and 4) whether the public interest would be furthered by the injunction. See Mova Pharm. Corp. v. Shalala, 140 F.3d 1060, 1066 (D.C. Cir. 1998). However, “the party seeking a preliminary injunction need not prevail on each factor.” R.J. Reynolds Tobacco Company, Inc. v. U.S. Food and Drug Administration, 11-1482, at 9 (November 7, 2011 D.D.C.). Rather, the court “appl[ies] the factors on a sliding scale.” Id. As a result, “if the arguments for one factor are particularly strong, an injunction may issue even if the arguments in the other areas are rather weak.” Id.

More specifically, the tobacco companies alleged that the requirement to place graphic images on its labels unconstitutionally compels speech. Generally speaking, compelled speech is presumptively unconstitutional and will only be upheld if it passes “strict scrutiny,” i.e.: 1) the government has a compelling interest it seeks to protect; and 2) the regulation is narrowly tailored to achieve that interest. However, as explained by the Court, narrow exceptions apply in the area of commercial speech. The government may require disclosure of only “purely factual and uncontroversial information” to protect consumers from “confusion or deception,” unless such a disclosure is “unjustified or unduly burdensome.” A lower level of scrutiny applies in cases where government- compelled speech meets this narrow exception.

In this case, the Court determined that the FDA’s rule did meet the narrow exception for compelled commercial speech for several reasons. First, the Court found that the images could not be considered purely factual because must were either digitally enhanced or manipulated to depict the negative consequences of smoking. Second, the Court found that the FDA’s argument that the images chosen by the rule were uncontroversial and purely factual was undermined by the fact that the FDA’s selected graphic images were designed to evoke viewers emotions. Finally, the Court found that when the graphic images were combined with the textual warnings and the mandatory display of the 1-800-QUIT-NOW smoking cessation hotline, the goal was to induce the viewer to quit or never start smoking. Thus, the Court found that the FDA’s labels were neither purely factual nor uncontroversial. Therefore, strict scrutiny and not a lower, more-deferential level of scrutiny applied.

In evaluating whether the FDA’s labeling rule passed constitutional muster, the Court found that regardless of whether the government’s interest in providing information to consumers is compelling, the FDA’s rule is not narrowly tailored to achieve such a purpose. The Court noted that the size and display requirements of the rule — the top 50% of the front and back panels of all cigarette packages and the top 20% of printed advertising — is not narrowly designed to achieve an informative purpose. Rather, the Court found that such dimensions promote a government sponsored anti-smoking message. Additionally, the Court found that the graphic warnings when combined with the textual messages and the 1-800 number result in the FDA “conscript[ing] tobacco manufacturers into an anti-smoking brigade.” Thus, the Court found that the tobacco manufacturers have a substantial likelihood of success on the merits because the FDA’s labeling requirements are likely to be found violative of the First Amendment.

The Court also found that the plaintiffs satisfied the other prongs necessary to be granted a preliminary injunction. The Court found that because of the plaintiffs’ likelihood of success on the merits and the fact that litigation would likely continue well beyond the September 2012 effective date, the plaintiffs would suffer irreparable harm if an injunction was not issued. Additionally, the Court found that injunctive relief would not harm any interested third parties because, based on the record, Congress did not demonstrate that such rules were urgent. In so finding, the Court noted that the Tobacco Act established a mutli-stage timeline in which the FDA was given two years to promulgate a Final Rule and a 15 month implementation period before the Final Rule took effect. Therefore, the Court found no prejudice to other third parties. Finally, the Court found that the “public interest will be served by ensuring that plaintiffs’ First Amendment rights are not infringed before the constitutionality of the regulation has been definitively determined.” As such, the Court granted the tobacco companies injunction.

Although the preliminary injunction is effective as of the Court’s order, the government does have the ability to file an interlocutory appeal challenging the Court’s decision. If the government does appeal and is successful, then the District Court’s preliminary injunction will be vacated. A similar situation arose in Sherley v. Sebelius, a case involving a challenge to federal funding for stem cell research. In that case, the plaintiffs were granted a preliminary injunction to prevent the NIH funding guidelines from taking effect. However, as we previously reported, the D.C. Circuit vacated the preliminary injunction on appeal and remanded the case to the district court for resolution on its merits.

The practical effect of a successful government appeal would be that, although tobacco companies would still be able to challenge the FDA’s rule on the merits, the companies would still have to comply with the FDA’s new labeling requirements starting September 2012.

Fuerst Ittleman will continue to monitor the progress of this lawsuit and the FDA’s regulation of tobacco products and advertising. For more information, please contact us at contact@fuerstlaw.com.

On November 3, 2011, GlaxoSmithKline (GSK) agreed to a settlement with the U.S. Department of Justice (DOJ) for a record-breaking $3 billion. The settlement, which is expected to be finalized in early 2012, involves multiple civil and criminal claims filed against GSK for the alleged off-label marketing of its widely controversial diabetes drug Avandia. In particular, the government alleged that GSK had illegally marketed Avandia for uses that were not approved in the product’s labeling.

The government’s prohibition of “off-label” marketing, or promoting a drug for uses other than those approved by the U.S. Food and Drug Administration (FDA), is a highly-contentious issue. While it is widely accepted that licensed practitioners may prescribe drugs for uses other than those approved by the FDA, drug manufacturers are prohibited from marketing such uses, even where the new uses show no signs of adverse events. However, although the FDA views its prohibition on off-label promotion as well-settled, challenges by drug manufacturers have called the legal grounding of this prohibition into question. Recently, various pharmaceutical manufacturers have brought challenges against the FDA regarding restrictions on off-label promotions, arguing that the prohibition violates the First Amendment. In addition, as previously reported, drug manufacturers petitioned the FDA in July 2011 requesting that the Agency solidify its stance on off-label marketing by promulgating regulations and publishing other guidance in this area.

For more information on FDA regulations and acceptable pharmaceutical marketing practices please contact us at contact@fuerstlaw.com.

On October 13, 2011, Senator Amy Klobuchar introduced a bill before the United States Senate, entitled the “Medical Device Regulatory Improvement Act.” Found here, the bill is aimed at amending the Federal Food, Drug and Cosmetic Act (FDCA) in an effort to increase efficiency in the way medical devices are reviewed by the U.S. Food and Drug Administration (FDA). In particular, the bill seeks to require the FDA to consider alternative ways of determining device safety and effectiveness, by requiring the agency to consider “alternatives to randomized, controlled clinical trials, such as the use of surrogate endpoints.” Additionally, the bill states that the FDA “shall not request information unrelated or irrelevant to a demonstration of reasonable assurance of device safety and effectiveness.” While the FDA often requests that manufacturers provide clinical data and other documentation under what it characterizes as “related to safety and effectiveness,” it is unclear how the bill would change the way the FDA reviews medical devices in practice.

As we previously reported, another bill proposing to change the way medical devices are reviewed was recently introduced before the U.S. House of Representatives. Similar to the bill proposed by Senator Klobuchar, the House bill is aimed at increasing the efficiency of FDA’s review process. However, the Senate bill differs inasmuch as it focuses primarily on expediting review for devices following the premarket approval (PMA) and 510(k) clearance pathways. Although the “Least Burdensome” provisions – the portion of the FDCA that the Senate bill seeks to change – have been in place since the passage of the FDA Modernization Act of 1997, many in the industry have found that the provisions have little effect on the FDA review process. Thus, many are hoping that the passage of the Senate bill will lead to greater efficiency by lessening the burden on manufacturers during the medical device review process.

These proposals to update FDA’s medical device review process are largely a result of the report recently released by the Institute of Medicine (IOM). Published on July 29, 2011, the IOM Report contained various recommendations for the FDA in relation to its medical device review process. As we previously reported, the IOM particularly took issue with FDA’s 510(k) review process, recommending that the system undergo a complete overhaul.

Fuerst Ittleman will continue to monitor the developments and changes to FDA’s medical device review process. For more information, please contact us at contact@fuerstlaw.com.