Senate passes Food Safety Crime Bill with greatly enhanced penalties

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The United States Senate recently passed a food safety crime bill sponsored by Senator Patrick Leahy that will significantly strengthen criminal penalties for companies and persons that knowingly violate food safety standards and place tainted products on the market. The legislation, known as the Food Safety Accountability Act, will create a new criminal offense in Title 18 of the United States Code, and will have significant criminal penalties of up to 10 years imprisonment for committing certain food offenses “knowingly and intentionally to defraud or misleadand with conscious or reckless disregard or a risk of death or serious bodily injury.” The Senates version will now go to the House of Representatives for consideration. This bill evidences the Governments increased focus on food safety and adds teeth into the new Food Safety Modernization Act, passed last year to increase the regulatory powers and oversight of the Food & Drug Administration.

The FDA is ramping up criminal enforcement of the nations food and drug laws. We have previously blogged about the unsuccessful prosecution of the general counsel of GlaxoSmithKline, a large pharmaceutical company for obstruction of justice, here. We have also recently blogged here on the new emphasis by the FDA on bringing Park doctrine prosecutions, where corporate executives can be convicted of crimes even if they have no knowledge of or intent to commit a crime. Our lawyers are monitoring the progress of this bill and are ready to advise clients on how to navigate the FDAs regulatory minefield.

Induced Pluripotent Stem Cell Treatment Suffers a Setback

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In a study published in Nature, researchers report that tissues made from induced pluripotent stem cells, or iPS cells, might be rejected by a patients immune system, even when the tissue is transplanted into the same person from which the cells were made. Induced pluripotent stem cells are adult stem cells that have been genetically reprogrammed to have the pluriopotency character of embryonic stem cells. This means the iPS cells can theoretically be reprogrammed to grow into different types of tissue, such as nerve, heart, liver, or other types of tissue.

When initially invented in 2007, iPS cells held promise for the regenerative medicine field because they held advantages over embryonic stem cells and other adult stem cells. The two major advantages over embryonic stems cells were that these cells were not controversial because they were adult stem cells and did not require the destruction of human embryos and it was assumed that the tissues created from the patients own iPS cells would not be rejected by that patients immune system. The pluripotency character of these cells created the advantage over other adult stem cells. This study has finally tested the latter assumption.

The study was led by Yang Xu, a molecular biologist at the University of California, San Diego. When Xus team transplanted the iPS cells into genetically identical mice, the iPS cells made from mouse skin cells were rejected by the immune systems of those mice. It is not clear if the same results would hold true in humans, but other scientists assume they would.

Although this study may create a setback for regenerative medicine, iPS cells are still a valuable research tool. Many scientists are using iPS cells to create cells (for example, nerve cells from someone with Parkinsons disease) that can be used to study diseases and treatments in the laboratory.

Fuerst Ittleman recognizes the promise that stem cells hold for regenerative medicine. We will continue to monitor future studies with iPS cells and other stem cells. For more information the regulatory oversight of stem cells, contact us at contact@fidjlaw.com.

Former in-house counsel for GlaxoSmithKline acquitted

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In another stunning and surprising ruling to come out of the prosecution of Lauren Stevens, a former in-house counsel for GlaxoSmithKline, for obstructing an FDA investigation into off-label marketing, the Court granted Ms. Stevens motion for a judgment of acquittal after the end of the presentation of the governments case at trial. Essentially, the Court found the evidence legally insufficient to have a jury consider it. The transcript of that decision can be found here. We previously blogged about the Stevens prosecution here and here.

What is notable about the Courts decision to acquit Ms. Stevens is not only the rarity of such acquittals before a jury gets to deliberate, but what the Court stated about the importance of the attorney-client privilege. Ms. Stevens was prosecuted for conduct during the course of her work responding to an FDA investigation as an in-house lawyer for a major pharmaceutical company. The Court found that many of the documents used as evidence by the government should never have been provided to it under the attorney-client privilege. Those documents were provided by GlaxoSmithKline under an exception to the attorney-client privilege involving cases where a lawyer is retained specifically to assist a client to commit a crime or a fraud. The Court found that Ms. Stevens was never retained or appointed for that purpose, but to provide representation to the corporation and to gather information. Therefore, the exception to the attorney-client privilege was inapplicable, and the government should never have had access to otherwise privileged documentation.

The Court also expressed a concern regarding possible abuses in permitting the prosecution of a lawyer for providing legal guidance. The Court stated that it had sentenced a number of lawyers who actually committed crimes or assisted others in committing crimes. This was not one of those cases. The Court stated that lawyers, “should never fear prosecution because of the advice that he or she has given to a client”, and that “a client should never fear that its confidences will be divulged unless its purpose in consulting the lawyer was for the purpose of committing a crime or a fraud”. This decision is important to businesses and individuals alike, in that it reaffirms that the government cannot invade the space between a lawyer and his or her client except under very narrow circumstances, none of which were applicable in the case of Ms. Stevens.

The Court also clearly rejected the governments theory of prosecution”that Ms. Stevens acted to obstruct justice. Instead, the Court reviewed Ms. Stevens conduct in zealously representing her client and placed it in the most favorable light in the investigation. Also, the Court found that the allegedly false statements to the FDA attributed to Ms. Stevens were taken out of context and were made under the advice of numerous lawyers for the company. The Court stated that “only with a jaundiced eye and with an inference of guilt thats inconsistent with the presumption of innocence could a reasonable jury ever convict this defendant”.

The government, including the FDA, has made it a priority to prosecute not just corporations, but also individuals in regard to the commission of strict liability criminal violations of regulatory laws. These so-called “Park” prosecutions have been discussed in our blogs here and here. The Stevens prosecution was not a “Park” prosecution because it alleged intentional, willful conduct, but it highlights the governments goal of prosecuting and convicting more individuals, not just companies, of criminal violations of regulatory laws. Our White Collar Criminal Practice group continues to monitor these cases in our effort to keep our clients informed and out of harms way.

Second Patient Receives Embryonic Stem Cell Treatment in Gerons Clinical Trial

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Geron Corp. has announced, as part of its landmark Phase I clinical trial, that a second patient has received an embryonic stem cell injection. The patient, who recently suffered a severe spinal cord injury, received the injection at Northwestern Memorial Hospital and will undergo rehabilitation at the Rehabilitation Institute of Chicago. In August, 2010, we reported that the U.S. Food and Drug Administration (FDA) announced the “go ahead” for the worlds first authorized human trial of an embryonic stem cell treatment.

The purpose of the trial is to establish the safety of the embryonic stem cells, in addition to establishing that the cells will effectively travel to the site of a recent spinal cord injury and help restore the damaged nerves. The team will look to see if the stem cells improve the patients control or sensation in the trunk or legs.

The first patient to undergo the procedure, over six months ago, has not had any serious side effects. However, it is still too early to determine whether the patients control or sensation has improved.

Court Dismisses Mylan Pharmaceuticals Lawsuit Over Lipitor Generic ANDAs On Standing and Ripeness Grounds

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On May, 2, 2011, the United States District Court for the District of Columbia granted the FDAs Motion to Dismiss a lawsuit brought by Mylan Pharmaceuticals (“Mylan”) seeking injunctive and declaratory relief for alleged violations of the Administrative Procedure Act (“APA”) by the FDA in the approval process of several Abbreviated New Drug Applications (“ANDA”) for the brand-name drug Lipitor. A copy of the Courts decision can be read here.

The decision contains a helpful and educational summary of the FDA approval process for generic drugs. As explained within the opinion, once a brand-name or “pioneer drug” has received approval, manufacturers of generic versions of these drugs may seek approval of the FDA to market their generic versions by filing an ANDA.

Within the ANDA, a generic drug manufacturer must demonstrate that the generic is the “bioequivalent” of the pioneer drug, i.e. the new generic drug can be expected to have the same therapeutic effect as the pioneer drug when administered to patients. Additionally, for each “Orange Book” patent of the pioneer drug that is implicated by the generic drug, the generic manufacturer must certify as to whether the proposed generic would infringe on that patent. If an ANDA applicant seeks to market its generic drug prior to the expiration of the patents for the brand name drug, it must make a “paragraph IV” certification stating “such patent is invalid or will not be infringed by the manufacture, use, or sale, of the new drug. . . .” 21 U.S.C. § 355(j)(2(A)(vii)(IV).

However, once a generic drug manufacturer has filed an ANDA with a paragraph IV certification, it has by law infringed on the underlying patents and the brand-name drug manufacturer may bring a patent infringement suit. As a result, challenging patents can be costly for generic manufacturers. To encourage the production of generic drugs, federal law provides the first generic drug manufacturer who files an ANDA containing a paragraph IV certification, whose ANDA is ultimately approved by the FDA, a 180 day exclusivity period in which it may manufacture its generic version free from competition from other generic manufacturers. 21 U.S.C. § 355(j)(5)(B)(iv).

The Mylan case stems from competing ANDAs for the production of a generic equivalent of Lipitor. Plaintiff, Mylan Pharmaceuticals, through its subsidiary Matrix labs, filed an ANDA for its generic of Lipitor two years ago and, at the time of the suit, the FDA was still evaluating its application for approval. Mylan argued that its generic should be eligible for approval and marketing by June 28, 2011 when the exclusivity on Lipitor patents begin to expire.
In this case, Mylan also alleged that a competitor, Ranbaxy Laboratories, Ltd. (“Ranbaxy”), whose own ANDA for a generic equivalent of Lipitor was filed nine years prior to the suit, was the first generic manufacturer to file an ANDA with a paragraph IV certification for Lipitor, therefore making Ranbaxy eligible for the 180 exclusivity period should its product become approved. Mylan further alleged that Lipitors manufacturer Pfizer and Ranbaxy reached a patent infringement settlement that prohibits the production of a generic equivalent by Ranbaxy until November 2011.

As a result of this settlement, and the additional 180 exclusivity period that Ranbaxy would be entitled to should its ANDA be approved, Mylan would be unable to market is product until May 2012. Mylan further argued that Ranbaxy should be stripped of its 180 day exclusivity period for violations of the FDA application integrity policy (“AIP”). The AIP was developed by the FDA to ensure validity of data submissions called into question by the agency’s discovery of wrongful acts such as fraud, untrue statements of material fact, bribery, and illegal gratuities and to withdraw approval of, or refuse to approve, applications containing fraudulent data. More information on the FDAs AIP can be found on the FDAs website here.

The case addressed whether drug manufacturers can sue the FDA and force the agency to take action on pending ANDAs filed by their competitors. Mylan brought its action against the FDA alleging two counts: 1) the FDA violated the APA by unreasonably or unlawfully delaying a determination that Ranbaxy violated the integrity policy; and 2) the FDAs failure to approve Mylans ANDA on the basis of Ranbaxys 180 exclusivity violated the APA because it is arbitrary and capricious. In response, the FDA Filed a Motion to Dismiss for lack of subject matter jurisdiction.

In rejecting Mylans arguments and granting the FDAs Motion to Dismiss, the Court focused on standing and ripeness, two basic requirements lawsuits. Put simply, standing is the right of a person to bring a case. In order to establish standing, a plaintiff must demonstrate: 1) that it has suffered an injury in fact, which is an actual or imminent invasion of a legally protected, concrete and particularized injury; 2) causation, i.e. the alleged injury must have been caused by the defendants conduct at issue; and 3) redressability, i.e. the court can provide a remedy to rectify the injury. Lujan v. Defenders of Wildlife, 504 U.S. 555, 560-561 (1992).

In determining that Mylan lacked standing, the Court found that because Mylans ANDA had yet to be approved it faced no imminent injury from the FDAs possible approval Ranbaxys ANDA and 180 day exclusivity period. Further, the Court found that no case within the D.C. Circuit has ever granted standing to a drug manufacturer who was a subsequent ANDA filer and who has not yet received FDA approval to compel the FDA to take action on a competitors ANDA.

Additionally, the Court went on to find that even if Mylan could assert an imminent injury, it still lacked standing because its injury could not be redressed by the relief it requested. As stated above, Mylans own ANDA has not yet been approved by the FDA. Therefore, even if the Court granted the relief Mylan requested, denying Ranbaxys ANDA and extinguishing its 180 day exclusivity period, Mylan could be no more certain that its own generic could begin being marketed in June 2011.

The Court went on to hold that even if Mylan could establish standing to sue the FDA, the case must still be dismissed because it was not ripe. The ripeness concept is closely related to the idea of standing to sue. In order to determine whether a controversy is ripe, the court must “evaluate both the fitness of the issues for judicial decision and the hardship to the parties of withholding court consideration.” Texas v. United States, 523 U.S. 296, 301 (1998).

Here, the Court found that the case was not ripe for two reasons. First, because Mylans own ANDA had not yet received approval from the FDA, factual uncertainty remained. As stated by the Court, “a claim is not ripe for adjudication if it rests upon contingent future events that may not occur as anticipated.” Further, the Court found that because the FDA has not yet acted, there was no final agency action, which is a required element for review under the APA. Finally, the Court found that any hardship Mylan might suffer by a delayed exclusivity determination was hypothetical because Mylans ANDA has not yet been approved. However, the Court did note that “nothing prevents Mylan from seeking judicial recourse if and when the FDA renders a final exclusivity decision that is not to Mylans liking.”

This decision places Mylan in a very difficult position. We will monitor this case as it makes its way to the D.C. Circuit Court of Appeals and will report when and if this decision is upheld on appeal. For more information regarding the ANDA generic drug approval process or for any questions regarding how your company can maintain FDA regulatory compliance, please contact us at contact@fidjlaw.com.

FDA Issues First New Rules under the Food Safety Modernization Act

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The U.S. Food and Drug Administration (FDA) today issued the first rules under the FDA Food Safety Modernization Act (FSMA). As we previously reported, President Obama signed the FSMA in January of this year to help ensure the safety and security of foods in the United States. The first rule gives the FDA the ability to administratively detain food for up to 30 days. The second rule requires that food importers declare whether the food products, including food for animals, have been denied entry into any other country. The final rules will become effective July 3, 2011. Interested persons may submit comments by August 3, 2011.

The first interim final rule issued under the FSMA gives the FDA the ability to administratively detain food the Agency believes has been produced under insanitary or unsafe conditions. Once the rule becomes final, the FDA will be able to detain food products that it has reason to believe are adulterated or misbranded for up to 30 days. The products will be kept out of the marketplace while the FDA determines whether an enforcement action, such as seizure or federal injunction against the distribution of the product in commerce, is necessary.

Previously, the FDA only had the authority to detain food products when it had credible evidence that a food product presented was contaminated or mislabeled in such a way that it presented a threat of serious adverse health consequences or death to humans or animals. In order to pursue enforcement, the FDA would often work with state agencies to embargo a food product under the states legal authority until federal enforcement action could be initiated in federal court.

Under the second interim final rule, anyone importing food into the United States will be required to inform the FDA if any country has refused entry to the same product, including food for animals in addition to any other information already required. The new requirements in this notice allow the FDA the ability to better identify imported food shipments that may pose safety and security risks to consumers in the United States. This new reporting requirement will be administered through the FDAs prior notice system for incoming shipments of imported food established under the Public Health Security and Bioterrorism Preparedness and Response Act of 2002.

In a press release issued by the FDA, FDA Deputy Commissioner for Foods Mike Taylor said, “[t]he new information on imports can help the FDA make better informed decisions in managing the potential risks of imported food entering the United States.” According to Taylor, “[t]hese rules will be followed later this year and next year by a series of proposed rules for both domestic and imported food that will help the FDA continue building the new food safety system called for by Congress.”

Fuerst Ittleman will continue to monitor new rules issued by the FDA under the FSMA. For more information regarding the new rules, please contact us at contact@fidjlaw.com or (305) 350-5690.

Two Pharmaceutical Companies File Lawsuits in Response to FDA’s DESI Decisions

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We recently reported the U.S. Food and Drug Administrations (“FDAs”) announcement of its intent to remove approximately 500 unapproved cold, cough, and allergy drugs from the United States market. As a result, on April 29, 2011, ECR Pharmaceuticals (“ECR”) and Laser Pharmaceuticals, LLC (“Laser”) filed Petitions for Review with the U.S. Court of Appeals for the District of Columbia Circuit pursuant to 21 C.F.R. § 514.235(b) and 21 U.S.C. § 355(h), which permits a direct appeal to an appellate court within 60 days after the entry of a relevant FDA order. The Petitions for Review requested the court to review and set aside the two final orders of March 3, 2011 that certain marketed unapproved cold, cough, and allergy drug products are not Generally Recognized as Safe and Effective (“GRASE”). The first order announced that all outstanding hearing requests pertaining to oral prescription drugs offered for the relief of cough, cold, or allergy symptoms had been withdrawn and any shipment of those products not approved under a new drug application (“NDA”) or abbreviated new drug application (“ANDA”) (other than an over-the-counter (“OTC”) product that complies with an applicable OTC monograph) is unlawful. In the second order, the FDA announced that it would take enforcement action against unapproved and misbranded oral cold, cough, and allergy prescription drugs and the persons who manufacture or cause the manufacture of those drug products.

As background, many of the drug products covered by the March 3, 2011 orders contain active ingredients that were originally introduced into the United States marketplace without a prior review as to effectiveness. The Federal Food, Drug, and Cosmetic Act (“FDCA”), as originally enacted, required the sponsor of a new drug demonstrate that the product was safe. New drugs did not have to demonstrate effectiveness. In 1962, Congress amended the FDCA and required new drugs to be proven effective, as well as safe. The amendment also require the FDA to conduct a retrospective evaluation of effectiveness for all drugs approved as safe between 1938, the year the FDCA was enacted, and 1962. To assist with the evaluation of effectiveness for over 3,400 products, the FDA contracted with the National Academy of Sciences/National Research Council (“NAS/NRC”). The NAS/NRC submitted reports to the FDA that were then published in the Federal Register. The FDAs implementation of the NAS/NRC reports was called the Drug Efficacy Study Implementation (“DESI”). Many of the active ingredients in the March 3 orders were reviewed for effectiveness through the DESI process.

All drugs covered by the DESI review are “new drugs” under the FDCA. If the FDA DESI decision classifies a drug as ineffective for one or more indications, that drug product and those drugs that are identical, related, or similar (“IRS”) to it can no longer be marketed for those indications and are subject to enforcement actions as an unapproved new drug.

In ECR Pharmaceuticals v. Commissioner of Food and Drugs, Case No. 11-1120, ECR states that its Lodrane® products are “identical, related, or similar (“IRS”) to the antihistamine/decongestant reformulation of Dimetapp Extentabs containing 12 mg of brompheniramine maleate and 75 mg of phenylpropanolamine hydrochloride in a controlled-release form.” ECRs Lorane® products are extended-release drug products that contain brompheniramine maleate alone or in combination with pseudoephedrine hydrochloride and are indicated as either an antihistamine or an antihistamine/decongestant drug product.

Laser Pharmaceuticals, LLC v. Commissioner of Food and Drugs, Case No. 11-1121, involves methscopolamine nitrate. According to the Petition for Review, The FDA has concluded that methscopolamine nitrate is not GRASE. In addition, the FDA has determined,

that products containing the active moiety in methoscopolamine nitrate that are marketed for the relief of cold, cough, or allergy symptoms are new drugs within the meaning of § 201(p) of the Federal Food Drug and Cosmetic Act, and therefore require approved new drug applications or abbreviated new drug applications prior to marketing. [FDA] further states that it intends to take immediate enforcement action against persons who market methscopolamine nitrate, as well as against those who manufacture the product or cause it to be manufactured or shipped in interstate commerce.

Both ECR and Laser cases were preceded with April 1, 2011 Petitions for Reconsideration/Petitions for Stay of Action. ECRs Petition for Reconsideration/Petition for Stay of Action asked the FDA to review and reverse its determination that ECRs Lodrane® products are not GRASE. If the FDA maintains its position, ECR ask the FDA to stay the effective dates for action for six months. ECRs Petition further adds that FDA has not appropriately considered all of the evidence and its actions fail to provide ECR with “the procedural protections in accordance with due process of law.” In Lasers Petition for Reconsideration/Petition for Stay of Action (CREATE A HYPERLINK), Laser requests that the FDA “delay any enforcement action against [Laser] for the manufacture of drug products containing methscopolamine nitrate until January 1, 2012, and delay any enforcement action for the shipment of such products until February 28, 2012.

The FDA has not responded to either Petition for Reconsideration/Petition for Stay of Action.

U.S. Patent and Trademark Office Grants Patents for Methods of Making Stem and Regenerative Cell-Enriched Fat Grafts

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The U.S. Patent and Trademark Office recently granted a patent (U.S. Patent No. 7,901,672) for a method of enriching a patients own fat with their own adipose derived stem and regenerative cells (ADRCs) to create a cell-enriched fat graft. The patent is broad in that it does not limit the method of obtaining stem and regenerative cells or the way the fat is enriched with the cells. The patent covers both manual and automated methods of making cell enriched fat grafts. For example, the patented method covers the collection of cells that have been collected from the fat tissue by enzymatic digestion or mechanical force and cells concentrated by density, filtration, or centrifugation. Under this patent, the cell-enriched fat graft many be prepared manually or in a device.

Sherley V. Sebelius: Federal Appeals Court Vacates Preliminary Injunction on NIH Funding for Embryonic Stem Cell Research

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Today, the United States Court of Appeals for the District of Columbia overruled, 2-1, a district court judges preliminary injunction on federal funding of research using embryonic stem cells (ESCs). Two scientists brought this suit to enjoin the National Institute of Health (NIH) from funding research using ESCs pursuant to the NIHs 2009 Guidelines. Opinion ( Opin.) at 2.

The district court had granted the plaintiffs motion for a preliminary injunction, reasoning that the scientists would likely prevail in demonstrating that the NIH Guidelines violated the Dickey-Wicker Amendment. The Dickey-Wicker Amendment is an appropriations rider that the NIH from funding:

  • (1) The creation of a human embryo or embryos for research purposes; or
  • (2) research in which a human embryo or embryos are destroyed, discarded, or knowingly subjected to risk of injury or death greater than that allowed for research on fetuses in utero under 45 C.F.R. 46.204(b) and section 498(b) of the Public Health Service Act (42 U.S.C. 289g(b)).

Opin. at 4.

The plaintiffs in this case, Dr. Sherley and Dr. Deisher, are scientists who conduct research using only adult stem cells. These scientists assert that the NIH violated the Dickey-Wicker Amendment by funding ESC research projects. Id. The plaintiffs had originally filed suit with several other individuals and organizations in August 2009. As we previously reported, the district court granted the Governments motion to dismiss due to a lack of standing. However, the plaintiffs appealed and the federal appeals court held that the doctors alone had standing because they competed with ESC research for funding from the NIH. Opin. at 7.

On remand, the district court granted the doctors motion for a preliminary injunction “providing Ëœthat defendants and their officers, employees, and agents are enjoined from implementing, applying, or taking action whatsoever to the [2009 Guidelines], or otherwise funding research involving human embryonic stem cells as contemplated in the Guidelines.” Id.

The Government appealed the district court decision. The appeals court found that the NIH reasonably concluded that government funding for ESC research pursuant to the 2009 Guidelines is not prohibited by the Dickey-Wicker Amendment. The Court reasoned that barring funding would be detrimental to ESC research by preventing new research projects and hindering projects that are currently underway. Circuit Judge Ginsburg, writing for the Court, reasoned that the NIH Guidelines accounted for the Dickey-Wicker Amendment by making distinctions between stem cells and embryos. Opin. at 6. Additionally, Judge Ginsburg reasoned that the Guidelines allow for federal funding of research on ESCs that are already in existence or have been created by private funding. The Guidelines state that federal funding cannot be used to fund the derivation of new cells lines which are obtained through the destruction of embryos.

The courts analysis turned on the ambiguity of the Dickey-Wicker Amendment, specifically, a lack of definition for the word “research.” Opin. at 13. The court determined that the present tense of the Amendment, with no reference to embryos that “were destroyed,” implied that the Amendment did not ban ESC research on stem cell lines in existence at the time of the Amendments enactment. Opin. at 11. Judge Ginsburg also pointed out that Congress has continued to leave the Dickey-Wicker Amendment unchanged every year since 1996 even though Congress has had “full knowledge” that the Department of Health and Human Services has been funding ESC research since 2001. Opin. at 16.

For now, the courts decision to vacate the preliminary injunction means that federal funding can continue while pending lawsuits challenging the expansion of ESC research continue.

Court Dismisses Drug Manufacturer’s Suit Against FDA Challenging Bioequivalence Regulations For Lack of Standing

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On April 15, 2011, Judge Ellen Segal Huvelle of the United States District Court for the District of Columbia granted the FDAs motion to dismiss a lawsuit brought by ViroPharma, Inc. (“ViroPharma”) under the Administrative Procedure Act (“APA”) challenging the FDAs Abbreviated New Drug Application (“ANDA”) bioequivalent regulations. A copy of the Courts opinion can be read here.

The case centered on the various methods by which a generic drug manufacturer can establish the bioequivalence of its generic drug to an already FDA-approved brand name drug. Under 21 U.S.C. § 355 (j), prior to marketing a generic version of a brand name or “reference listed drug” (“RLD”), a generic drug manufacturer must submit an ANDA. Within the ANDA a generic drug manufacturer must demonstrate that the generic is the “bioequivalent” of the RLD, i.e. the new generic drug can be expected to have the same therapeutic effect as the RLD when administered to patients. There are two standard methods by which bioequivalence is determined, in vivo, (human testing) and in vitro, (laboratory testing). However, under 21 U.S.C. § 355(j)(8)(C), where a drug is not intended to be absorbed into the bloodstream, the FDA may establish “alternative, scientifically valid methods to show bioequivalence if the alternative methods are expected to detect a significant difference between the drug and the [RLD] in safety and therapeutic effect.”

The lawsuit stems from a citizen petition filed in 2007 by another brand name drug manufacturer, in which it petitioned the FDA to require all ANDAs for generics of its drug include in vivo bioequivalence studies. In response to that petition, the FDA asserted that, based on 21 U.S.C § 355(j)(8)(c) and 21 C.F.R. § 320.24, it had discretion to accept in vitro studies if those studies are determined to be scientifically valid methods of showing bioequivalence.

In its Complaint, ViroPharma, a drug manufacturer of the brand name drug Vancocin, alleged that 21 C.F.R § 320.21 established a general requirement that bioequivalence be demonstrated through in vivo testing unless the drug product meets the waiver criteria in 21 C.F.R. § 320.22. ViroPharma alleged that, by announcing that it had discretion to accept in vitro or in vivo testing, the FDA amended its regulations regarding bioequivalence by “interpreting the list of bioequivalence methods provided in 21 C.F.R. § 320.24 as a separate and sufficient basis for waiving in vivo bioequivalence requirements independent of 21 C.F.R. § 320.22.” As a result, ViroPharma alleged that the FDA violated the Administrative Procedure Act by effectively amending its ANDA regulations without engaging in notice and comment rulemaking.

In the Courts Opinion granting the FDAs motion, Judge Huvelle found that ViroPharmas lawsuit must be dismissed because ViroPharma lacked standing, a basic requirement to bringing a case. Put simply, standing is the right of a person to bring a case. In order to establish standing, a plaintiff must demonstrate: 1) that it has suffered an injury in fact, which is an actual or imminent invasion of a legally protected, concrete and particularized injury; 2) causation, i.e. the alleged injury must have been caused by the defendants conduct at issue; and 3) redressability, i.e. the court can provide a remedy to rectify the injury. Lujan v. Defenders of Wildlife, 504 U.S. 555, 560-561 (1992). Additionally, in the context of a procedural rule challenge, such as in this case, a plaintiff must “show not only that the defendants acts omitted some procedural requirement, [here a lack of notice and comment as required by the APA], but also that it is substantially probable that the procedural breach will cause the essential injury. . . .” Crt. For Law & Educ. V. Dept of Educ., 396 F.3d 1152, 1157 (D.C. Cir. 2005).

In this case, ViroPharma alleged that as a result of the FDA allowing in vitro bioequivalence studies to be submitted by generic drug manufacturers, it has or would in the future suffer two injuries: 1) future lost profits from generic competition and 2) current harm to its ongoing business operations. However, the Court rejected both of these arguments. The Court found that it was not substantially probable that the FDAs actions in declaring that it had the discretion to accept either in vivo or in vitro bioequivalence studies caused any injury in the form of lost profits. The Court reasoned that ViroPharma has not and will not suffer any injury to lost profits as a result of the FDAs announcement unless and until: 1) the FDA actually approves a ANDA for generic versions of Vancocin and 2) such approval must be based upon an in vitro bioequivalence study that does not qualify for a waiver under 21 C.F.R. § 320.22. However, until such time as the FDA actually relies upon the challenged interpretation of 21 C.F.R § 320.24, the Court ruled that ViroPharma has not suffered an injury.

The Court also found that ViroPharma could not establish standing based on current harms to its business. The Court found that the alleged harms were too vague and not sufficiently “concrete and particularized” to establish an injury in fact. Additionally, the Court went on to find that even if such harms could establish an injury in fact, ViroPharma failed to demonstrate a causal connection between these harms and the FDAs announcement because “ViroPharma elected to take [these actions] in response to its own predictions about what the FDA may do in the future. . . .” As a result, ViroPharma could not establish the causation element necessary for standing.

For more information regarding the ANDA generic drug approval process or for any questions regarding how your company can maintain FDA regulatory compliance, please contact us at contact@fidjlaw.com.