FDA Lawyers Blog

by Brian Malkin

On February 22, FDA granted in part denied in part a citizen petition filed on behalf of Hoffman-La Roche ("Roche") requesting that FDA confirm that it will stay approval for Orchid Healthcare's ("Orchid's") abbreviated new drug application ("ANDA") for generic Boniva® (ibandronate sodium) consistent with the 30-month stay provisions. FDA's decision confirms its position taken in a draft guidance that conversion of a patent certification to approve an application following a patent's expiration (a "Paragraph III Certification") to a patent challenge (a "Paragraph IV Certification") can result in a new 30-month stay.

FDA Response to Generic Boniva Citizen Petition

Orchid originally submitted its ANDA for generic Boniva with both Paragraph III and Paragraph IV Certifications. Roche sued Orchid within 45 days of receiving Orchid's Paragraph IV Certification notifications, resulting in an initial 30-month stay. The stay was dissolved, however, when Roche dismissed its claims for infringement of the patents-at-issue. Orchid then converted its Paragraph III Certification to a Paragraph IV Certification, provided Roche with the applicable notice, and was sued within 45 days of such notice, resulting in the subsequent 30-month stay. Potentially complicating factors raised by Orchid in its response to Roche's petition were that Orchid filed its ANDA during the last year of Roche's new chemical entity exclusivity ("NCE") and the patent-at-issue was extended under 35 U.S.C. 156 following submission of Orchid's original ANDA.

FDA determined that Roche's NCE for Boniva® and its patent term extension for the patent that Orchid had subsequently filed a Paragraph IV Certification for did not change the applicable 30-month stay for the revised certification. FDA also said that the 30-month stay would expire with the expiration of the patent or if the patent infringement suit were resolved in favor of Orchid. FDA's decision appears, therefore, consistent with FDA's guidance and its prior position with how 30-month stays will expire when a patent expires.

PIVDisputes2011

American Conference Institute invites you to join your peers and colleagues at the 5th Anniversary Edition of its Paragraph IV Disputes conference. Ed Haug, Brian Malkin and Charlie Raubicheck from FLH will be presenting at this timely and industry-leading forum where counsel and advisors for brand name and generic pharmaceutical companies will address every facet of Paragraph IV litigation, in addition to some of the most pressing and recent controversies surrounding these cases:

• Double patenting obviousness
• Inducement of infringement
• Section 8 carve-outs
• Inequitable conduct
• Damages
• Possible re-evaluation of the invalidity standard

This event -- which is widely recognized for setting the standards for Paragraph IV litigation and which also serves as the annual meeting place for the "who's who" of pharmaceutical patent litigation -- is now the single forum on which brand name and generic companies can rely for answers during this turbulent time in which the balance of power designed by the Hatch-Waxman Act may completely unravel. Come to this conference and get the up-to-the minute information that you need to prepare for the new litigation confrontations to come.

Do not miss your opportunity to enhance your learning and networking experience by attending one or both of our hands-on, informative and practical workshops:

• Hatch-Waxman and BPCIA 101 -- A Primer on IP Basics and Regulatory Fundamentals
• The Master Class on Settling Paragraph IV Disputes: Drafting and Negotiating Strategies
for Brand-Name and Generics

For more information and to register, click here. FDA Lawyers Blog readers can obtain a $200 discount with the code FDALWY.

by Elizabeth Murphy

In early January, President Obama signed into law the Food Safety Modernization Act ("FSMA"), which instituted broad changes to the regulation of the nation's food supply. Equally sweeping but less publicized was a whistleblower provision contained within, providing protection for employees of the legislation's covered entities.

Section 402 of the FSMA applies broadly to any "entity engaged in the manufacture, processing, packing, transporting, distribution, reception, holding, or importation of food." The provision would prevent such an entity from discharging or taking adverse employment action in retaliation for certain protected activities. Protected activities covered by Section 402 include, among other things, reporting to internal or external (such as state or federal agencies) sources, or refusing to participate in, potential violations of the FSMA. With regard to the degree of certainty a whistleblower must have to receive protection under Section 402, the standard is fairly forgiving: all that is necessary is a reasonable belief that malfeasance is afoot.

The burden of proving causation also favors the whistleblower, as a complainant under Section 402 would only have to show that the protected activity was a "contributing factor" to the discharge or adverse employment action. In contrast, an entity defending itself under the provision would have to show by clear and convincing evidence that the same adverse employment action would have taken place regardless of the protected activity.

Though the protection does not extend to industries regulated by the U.S. Department of Agriculture (and, as such, does not cover meat and poultry workers), the implications for employers are broad in scope. As one legal analyst points out, the FSMA refers to the Federal Food, Drug, and Cosmetics Act. This could potentially mean that whistleblower protection could reach beyond food products, into the realm of drugs and cosmetics, even though the whistleblower provision is directed to the food handling and processing industries.

by Howard E. Rosenberg, Ph.D.

According to Shanghai Securities News last week, China will allocate billions of yuan to support domestic chemical and pharmaceutical companies in their development of overseas markets. The Chinese government has outlined a draft of the new policy where it may invest up to 5 billion yuan ($759.29 million) in the sector. According to reports, the policy will be released in the first half of this year.

During the 12th Five-Year Plan (2011-2015), China is expected to support more companies in their overseas certification to export products to the U.S., Japan, and Europe. The focus will be on improving companies' current good manufacturing practices ("cGMPs") to the levels adopted in these countries. Over 20 companies met the cGMP standards during the 11th Five-Year Plan, and it is thought that the future prosperity of China's chemical and pharmaceutical companies will depend on more of them meeting cGMPs. During the next five years, over a hundred companies are predicted to obtain these levels.

Yu Mingde, President of the Chinese Pharmaceutical Enterprises Association said, "In the next five years, the government will assist some 60 producers in the sector with the goal of reaching international quality standards of manufacturing, and also help the sector realize total export volume of more than $4 billion." The cGMP requirements adopted in Europe and the U.S. will be harder for Chinese drugs to meet, but, at the same time, once met, will benefit them more, added Yu.

China produces most of the world's active pharmaceutical ingredients ("APIs"), Guo Fanli, a pharmaceutical analyst with CIC Industry Research Center, was reported as saying last Thursday. "The majority of the API drugs produced in China are exported to Africa, since it is hard for Chinese drug producers to comply with the quality standards of Western countries," Guo said.

For a country the size of China to have just 20 companies producing APIs to cGMPs and to aim for only another 100 companies to achieve that standard over the next 5 years is surely inadequate. A vast amount of pharmaceutical intermediates already come out of China and presumably this suggests they are not being made to cGMPs. There have been several instances where contamination by impurities in Chinese APIs has led to deaths. For China to allay fears, not only domestically, and to restore confidence with the FDA, the European Medicines Association, and other health authorities, far more of an effort must be channeled locally into regular inspections of all those companies wishing to market pharmaceuticals and to ensure they always meet cGMPs.

FLH's Scientific Advisor Howard E. Rosenberg, Ph.D. will present on "International IP Developments" covering subtopics "Topical IP (intellectual property) cases", "EU (European Union), patents and SPCs" and "Review of other jurisdictions around the world" at the World Generics Medicines Congress Europe 2011 in London, United Kingdom. The Congress will be held at The Hilton London Paddington. Event details may be found here.

FDLI Policy Forum Vol 1, Issue 4

"Should FDA Undertake More Than a 'Ministerial' Role With Respect to Patent Information?" by Brian Malkin and Andrew S. Wasson can be found in FDLI's current Food and Drug Policy Forum. For many years FDA has argued that it lacks the resources and expertise to review patents substantively. FDA refers to its hands-off role as "ministerial." Indeed, many courts have upheld FDA's position. It is not the case, however, that courts have mandated that FDA take this position. In fact, several leading judges have questioned whether it is good policy. Therefore, the authors suggest that hiring a few competent patent attorneys, trained in biotechnology or the pharmaceutical sciences, could result in the more efficient administration of the Hatch-Waxman Act Amendments to the Federal Food, Drug, and Cosmetic Act. The authors do not believe that adding these individuals to FDA's staff would be unduly burdensome.

The timing of the article may not be the best-word from GPhA's Annual Meeting 2011 is bleak regarding FDA's always-epic workload-but the authors believe that it is important to underscore that a more direct way to administer the statute exists.

FDA Lawyers Blog also would like to introduce its readers to FDLI's new Food and Drug Policy Forum. FDLI's Food and Drug Policy Forum is a peer-reviewed venue for the examination and discussion of pressing policy issues in food and drug regulatory law. FDLI published the first issue in January of this year. FDLI's Food and Drug Policy Forum includes an electronic discussion space for refining and debating ideas-so if you'd like to join in the discussion, commenting is encouraged--and the authors will be watching and responding!

by Erin A. Lawrence

On February 14, the European Commission Joint Research Center, based in Italy, launched a repository of nanomaterials with a representative range of 25 different types of reference nanomaterials. This will support the safety assessment to ensure consumer protection and products by enabling harmonized risk assessment. This event follows on a meeting held by the European Commission in 2010 to determine the definition of nanomaterials to be used in European legislation.

Nanotechnology is the science of controlling molecular structures comprised between 1 and 100 nanometers. The size of the nanomaterials gives them different chemical, physical, and biological characteristics than the larger form of the same--the reason distinct policies are required. For instance, the increased surface-to-volume ratio of these materials increases their chemical reactivity. Nanomaterials are used in various consumer products and industrial materials.

The Scientific Committee on Emerging and Newly Identified Health Risks ("SCENIHR") provided advice on the essential scientific elements for defining the term "nanomaterials." SCENIHR gave three opinions. First, where the chemical properties and materials may change with size, there is no scientific justification for a single upper and lower size limit associated with these changes that can be applied to adequately define all nanomaterials. Second, there is scientific evidence that no single methodology can be applied to all nanomaterials. And third, size is universally applicable to define all nanomaterials and is the most suitable but size distribution is the most relevant consideration. SCENIHR expressed the need to develop a standardized method to determine the size of nanomaterials, their constituent parts, and their corresponding distribution to ensure the accuracy of comparison of nanomaterials.

For additional information on nanomaterials, see our earlier blog here.

by Brian Malkin

On February 16-18, approximately 500 industry executives and stakeholders attended GPhA's Annual Meeting in Orlando, Florida. During the public sessions to which this blog refers, representative generic industry chief executive officers ("CEOs") were somewhat optimistic with the potential for $150 billion of branded products coming off patents (coined a "patent cliff"). Yet the overall message was more negative, focusing on slower FDA approvals, less new innovator targets for generics with greater possibilities for preemption issues regarding failures to add warnings to generic drug labelings, and an uncertain biosimilars market to replace the small molecule opportunities that will be drying up.

Deborah Autor, J.D., FDA's Director of Compliance, Center for Drug Evaluation and Research, announced that the Office of Generic Drug's ("OGD's") more than 2000 application backlog was likely to continue and possibly worsen, in part due to FDA's inability to conduct the necessary pre-approval inspections for new drug applications--both innovator and generic. For example, Autor said that FDA anticipated that in fiscal year 2011, 192 foreign facility inspections will be required, but FDA will only be able to conduct 62. While generic application user fees could theoretically reduce approval times for new applications if FDA adopted a "surveillance model," Autor noted that inspections were a key reason why previous negotiations for user fees failed and could fail again. Autor added that this is compounded by the fact that there are roughly eight times the number of generic to innovator applications, and generic applications tend to have more multiple supplier or facility issues with less available data during inspections. Autor hoped FDA's message that corporate executives are accountable for FDA violations may improve the quality of generic record-keeping, including generic manufacturers obtaining better data from their suppliers.

On the generic industry side, there are greater opportunities for corporate accountability and a mixed bag for continued growth. Current legal trends suggest that leading generic applicants will likely be responsible for failures to add warnings to their products (the preemption issue). While generic growth was higher than total prescription growth (2.3 % versus 1.0%) based on market data, growth in traditional sectors such as cancer treatments were slow and other indicators showed that despite the patent cliff, the branded industry has been slow to innovate, leaving less future generic targets.

by Andrew M. Nason

Two proposals included in President Obama's 2012 budget could lead to increased competition between generic drugmakers and large brand-name pharmaceutical companies. One proposal would allow the Federal Trade Commission ("FTC") to stop controversial "pay-for-delay" settlements of drug patent challenges. A second proposal would speed up the availability of generic biologic drugs by cutting the marketing exclusivity of brand biologics from twelve years to seven years. Both proposals face a tough challenge to pass through the divided Congress, as similar proposals previously have run into tough opposition from lawmakers.

The budget seeks to eliminate "pay-for-delay" deals, under which brand-name and generic drugmakers settle patent challenges with payoffs to the generic challengers that delay lower-cost generic drugs from reaching the market. Both brand-name and generic manufacturers have defended the controversial deals, claiming they can lead to early introduction of generic drugs while eliminating the uncertainty of litigation. The Generic Pharmaceutical Association ("GPhA") called the proposal regarding the settlements "misguided." While the White House claims such a ban would save $8.8 billion in federal funds over the next ten years, GPhA believes the Congressional Budget Office used several faulty assumptions to arrive at this number. On the brand side, Pharmaceutical Research and Manufacturers of America ("PhRMA") president John J. Castellani stated, "the President's proposed restrictions on certain types of patent settlements could reduce incentives for future medical innovation. . . . Restricting such settlements, which already are subject to review by the [FTC] and Department of Justice, could discourage pro-consumer settlements that do not delay generic entry past patent expiration, but instead often bring generics to market years before patent expiration."

In contrast to the provision regarding settlements, the proposal regarding biologics predictably met with mixed reviews among generic and brand manufacturers. Biologics--medicines derived from proteins manufactured in living cells--can be far more complex and expensive to manufacture than traditional pharmaceuticals. The White House says its proposal "strikes a balance between promoting affordable access to medication while at the same time encouraging innovation to develop needed therapies." It also would save, according to White House estimates, $2.3 billion by 2021. GPhA lauded the proposal, saying "a 12-year exclusivity period would provide unwarranted monopolies for brand biopharmaceuticals, which would delay the savings that could result from the earlier introduction of biogenerics." PhRMA disagreed, stating that disrupting the current balance achieved by the biosimilars provision of the health care reform law could "seriously threaten innovative companies' ability to fund research on future treatments and cures."

by Richard F. Kurz

On February 22, final briefs are due in a controversy Cephalon stirred up in its lawsuit with the Federal Trade Commission ("FTC"). Underlying this controversy is an antitrust action brought against Cephalon after it settled a patent infringement suit with four generic pharmaceutical companies. However, unlike other antitrust actions against such settlements, which the FTC dubs "pay-for-delay," this case took an unusual twist.

In similar cases, the FTC and its expert witnesses typically rely on conclusions drawn from two FTC studies that reviewed settlement agreements between brand name and generic companies. Yet here, Cephalon surprised many when it asked the Court to order the FTC to hand over the analyses, source materials, and other documents used in those studies. Cephalon argues that "fundamental principles of fairness . . . entitle Cephalon to obtain the underlying materials to scrutinize the studies' conclusions and to be in a position to respond to their use . . . ." In the alternative, Cephalon asks that such studies not be offered into evidence or otherwise relied on in the case. Cephalon reasons that "the FTC cannot have it both ways, by affirmatively relying on the studies' conclusions yet simultaneously cloaking the underlying documents in a veil of secrecy."

Cephalon's request has generated considerable controversy. On January 18, the four generics involved with Cephalon's settlement filed a brief arguing, inter alia, that because the studies address "other actions by other companies in other cases" they are "fundamentally irrelevant" and biased, and should therefore be excluded. Additionally, several third-party pharmaceutical companies have asked the Court for a protective order barring the FTC from disclosing the documents. These third-parties note that the Cephalon's request encompasses hundreds of sensitive commercial documents filed with the FTC in compliance with federal law under statutory guarantees of confidentiality. They further note that dragging practically the entire pharmaceutical industry into Cephalon's dispute defies common sense and fairness, while placing the third parties at a significant competitive disadvantage because Cephalon's outside counsel and experts would gain access to the industry's sensitive information. The FTC's January 24 response echoes these sentiments, noting that the information is not relevant to Cephalon's dispute and that statutory protections prohibit such disclosure.

In reply, Cephalon states that "the solution to those concerns is not to deny Cephalon information it needs to defend itself, but to preclude the FTC from relying on the concededly irrelevant studies." Alternatively, Cephalon asks that the FTC be required to identify the conclusions and source materials from the studies it intends to use.

The Court has ordered that any additional memoranda related to this controversy must be filed by the February 22nd deadline. As the flurry of briefs demonstrates, Cephalon and the FTC are not the only parties interested in the Court's eventual decision.

FLH Partners James K. Stronski and Brian J. Malkin will attend the Generic Pharmaceutical Association ("GPhA")'s Annual Conference in Orlando, Florida, from February 16-18. More than 500 attendees will join Mr. Stronski and Mr. Malkin to gain insight on how the nation's health and regulatory issues will impact the generic industry. Each year, GPhA's Annual Conference features presentations by leading industry CEOs, economists and financial analysts, FDA regulators, and state and federal officials. By the end of the conference, attendees will understand the opportunities and challenges for the generic pharmaceutical sector in 2011. More information about the conference may be found here.

by Andrew M. Nason

Optivia Biotechnology Inc., a leading provider of in vitro transporter assay services, announced that it signed a collaboration agreement with the U.S. Food and Drug Administration ("FDA") to assess the effect of dietary supplements on key drug transporters. The collaboration aims to identify potentially harmful interactions between drugs and dietary supplements, such as a supplement interacting with acetaminophen or other drugs associated with liver toxicity. Estimates blame drug-induced liver toxicity for as many as five percent of all hospital admissions, and fifty percent of all acute liver failures. Drug transporters greatly influence the liver's disposition of a number of commonly used drugs, such as antibiotics, statins, and hypoglycemic agents.

Following a recent report from the International Transporter Consortium that identified the most clinically significant transporter-related drug-drug interactions, drug-nutrient interactions have become a growing area of interest for both the nutrition and pharmaceutical industries. As a starting point, Optivia and FDA will use Optivia's novel transporter technology platform to examine potentially harmful interactions between the most clinically relevant transporters and dietary supplements such as black cohosh, green tea, ginko biloba, kava, and usnic acid. The platform features polarized mammalian cell assays that closely model human biology.

"This project further advances Optivia's leadership position in the development of quantitative tools for optimizing the safety and efficacy of drugs," stated Yong Huang, Ph. D., president and chief executive officer of Optivia. "We are excited about this opportunity to expand the use of our technology to examine the role of dietary supplements in causing drug-related liver injury."

by Brian Malkin

On February 8, Teva Pharmaceutical Industries ("Teva") announced in an earnings call that the previous day--a week before Valentine's Day--it had submitted to FDA a supplemental new drug application ("sNDA") to market its Plan B® One-Step (levonorgestrel) emergency contraceptive tablet as an over-the-counter ("OTC") drug product. Plan B® (two pills), which was first approved in 1999, contains a higher dose of the hormone progestin that has been used in traditional birth control pills for decades. Plan B® One-Step is indicated to prevent a pregnancy from occurring when taken as a single pill up to 72 hours after sexual intercourse. Plan B® One-Step is currently available without prescription for patients 17 years and older, when distributed by a pharmacist.

Teva's sNDA was long awaited by proponents, such as the Center for Reproductive Rights "CRR"), who had originally filed a citizen petition to open OTC access to Plan B® in 2001, when FDA had originally limited non-prescription sales to women 18 years and older. While FDA has not ruled on the petition--and reportedly did not plan to until Teva or another suitable applicant filed a request for OTC status--CRR subsequently filed a contempt complaint for FDA failing to reconsider OTC availability following a March 2009 court order to permit sales to women 17 years old. Teva's Plan B® One-Step was approved on July 10, 2009.

Teva's Plan B® One-Step sNDA is on a 10-month review timeline, which could permit its product to reach pharmacy shelves by the end of 2011--in time for the New Year. If Teva obtains approval for its sNDA, it will likely receive three years of market exclusivity for its OTC product, based on the clinical studies that it reportedly submitted to obtain OTC approval. In particular, Teva reportedly conducted studies for how females between the ages of 11 and 16 would self select an emergency contraceptive drug under simulated OTC conditions.

by Andrew M. Nason

On February 2, the Patent Reform Act of 2011 (S. 23) cleared the Senate Judiciary Committee unanimously, marking this the third time since 2008 that the Judiciary Committee has reported a version of the legislation to the Senate floor. But the bill still contains controversial provisions that many expect will lead to a fierce debate. The Committee adopted an amendment during markup that removed language that would have codified the "objective recklessness" standard for willful infringement set forth in In re Seagate Tech., LLC. Other provisions affecting the pharmaceutical industry, such as the introduction of "supplemental examinations," remain intact.

The Generic Pharmaceutical Association ("GPhA") released a statement on February 3 expressing concern that the bill's supplemental examination provisions would severely weaken the current inequitable conduct standard. As the law stands today, a court can render a patent unenforceable if the applicant knowingly withholds information or makes material misrepresentations during the patent application process with the intent to deceive the examiner. The legislation would alter the current standard by allowing a patent owner to request supplemental examination prior to litigation, and exempting from future charges of inequitable conduct any patent owners who survived reexamination. As we previously reported, proponents believe this provision would strengthen patents, due to further examination, and reduce litigation costs because of the unavailability of the inequitable conduct defense.

GPhA argues that such a weakening of the current standard will increase the cost of pharmaceuticals for consumers. Generic drug producers commonly plead inequitable conduct as an equitable defense in litigations involving drug compounds. The supplemental examination provision would increase the incentives for innovators and brand companies to be dishonest when seeking patents, because they could gain immunity from inequitable conduct allegations by tricking the U.S. Patent and Trademark Office twice instead of once. By weakening the standard for inequitable conduct, GPhA argues the legislation makes it more difficult to challenge dubious patents and bring affordable generic medicines to the market. Sen. Charles Schumer (D-NY) indicated he had an amendment that would have removed the supplemental examination provision before the bill left the Committee, but he did not enter it during the mark-up.

by Christopher Gosselin

Color Chart?
Baxter has some work to do at its Jayuya Facility in Puerto Rico, after FDA's warning letter last month cited the facility for several good manufacturing practices violations, including a failure to thoroughly investigate numerous complaints about contamination and discolored products. In September, an equipment failure at the Jayuya facility led to the recall of 17 lots of product, including Clinimix® (Amino Acid in Dextrose), Clinisol® (Amino Acid), and Travasol® (Amino Acid). According to the warning letter, Baxter's investigations did not adequately address the causes of the recalls.

Baxter did implement at least one creative solution in response to the discoloration problem-it distributed a "color chart" to end users explaining when not to use Baxter's products based on product color. Not surprisingly, the color chart failed to amuse FDA. Baxter received a misbranding violation because the approved labeling fails to bear adequate directions for use. It seems Baxter never submitted either the color chart, or any underling analytical data, for FDA approval.

According to the warning letter, Baxter's "investigation concluded that the administering health care professionals (i.e., pharmacist, nurse, or physician) would identify any discoloration and prevent the usage of the drug product." "It is unacceptable," the warning letter continues, "to rely upon the health care professional to fulfill your Quality Control Unit responsibilities." "The end user should not be expected to make a determination of product safety and effectiveness based on a color chart ... [i]t is your responsibility to ensure that your products comply with their predetermined specifications to ensure their quality, safety, and effectiveness."

Although Baxter said that it continues to manufacture the products at issue and that they remain safe and effective if used in accordance with labeled instructions, you might not want to throw your color charts away just yet.

by Richard F. Kurz

As of today, generic pharmaceutical companies Synerx Pharma, Apotex, and Teva have each filed amicus briefs in the Microsoft v. i4i case before the U.S. Supreme Court. The Microsoft case questions the standard used by courts when deciding whether or not to invalidate a patent. Microsoft's argument, which is supported by Apotex and Teva, is that courts should lower the standard (i.e., the burden) required for a challenger to invalidate a patent under particular circumstances. Synerx Pharma goes a step farther and argues that the standard should be lowered for all validity challenges.

When an inventor applies for a patent at the U.S. Patent and Trademark Office ("USPTO"), an examiner considers evidence called "prior art" to determine whether the claimed invention is, in fact, new--meaning it is novel and non-obvious when compared to the prior art. Prior art includes patent applications, patents, and publications available to the inventor that teach the then-known state-of-the-art technology. A patent is granted when the prior art would not have taught how to make the invention. Once granted by the USPTO, a patent is presumed to be valid. Consequently, to invalidate a patent a challenger must prove by "clear and convincing evidence" that the patent should not have been granted because the prior art actually did teach how to make the claimed invention.

In their briefs, Apotex and Teva each offer arguments supporting Microsoft's position in the case. Microsoft argues that the clear and convincing evidence standard should be maintained only for prior art that the examiner actually considered when granting the patent. However, when a challenger presents evidence of different prior art, Microsoft argues that a lower standard should be used--called the "preponderance of the evidence" standard. Such a standard would make it easier for challengers to invalidate a patent because, according to Teva, it is "currently a rare occurrence" for an examiner have a complete prior art record when conducting an examination.

by Howard E. Rosenberg, Ph.D.

On February 7, Senator Amy Klobuchar (D-MN) and Bob Casey (D-PA) introduced legislation called the Preserving Access to Life-Saving Medications Act (S. 296) to provide FDA with new tools to deal with potential drug shortages. The focus will be to better enable coordination between the pharmaceutical industry, FDA, and health care providers, so patients do not lose access to the medications that they depend on. Currently, application holders are not required to alert FDA to potential shortages or explain the delays. "Knowledge is one of the most important tools for combating problems associated with drug shortages, which are a growing threat to public health in Pennsylvania and across the U.S.," said Sen. Casey

Senator Klobuchar has been urging FDA to deal with the "unprecedented" shortage of medications. There are apparently 178 drugs running in short supply this year, more than three times the number in 2005. These drugs are generally no longer covered by a patent monopoly and so are available through generic manufacturers. However, if the margin (profit) is too low, a manufacturer is not likely to take up production line time to cure the shortage if a better margin product is required. A manufacturer, nevertheless, will likely go on record that the reasons for non-availability are more demand than expected, a shortage of raw materials and production delays.

The drugs that run short in many cases do not have direct substitutes and may fall in the areas of cancer, antibiotics, analgesia, or anesthetics. "It's drugs that are potentially lifesaving or critically important in care," said Bona Benjamin of the American Society of Health-System Pharmacists. The painkiller morphine; amikacin, an antibiotic for serious bacterial infections; and carmustine, a chemotherapy drug, are among about 150 drugs in short supply, her group says. As a result, oncology patients may have to accept alternative chemotherapy regimens or delay their prescribed treatment.

Klobuchar said the legislation would give FDA the authority to require early notification from pharmaceutical companies when they decide to limit or discontinue production of prescription drugs. She also said that when there is an impending shortage of a drug, FDA should have the authority to establish an expedited process to approve substitute treatments or the importation of safe, clinically-equivalent drugs from outside the United States.

But with the increasing downwards pressure on generic drug pricing the situation is unlikely to improve and it may be that in order to ensure supply of these important pharmaceuticals some thought into a pricing structure needs to be contemplated.

by Erin A. Lawrence

On January 21, a federal appeals court upheld a lower court's dismissal of a lawsuit filed on behalf of all frozen human embryos in the U.S. that sought to halt federal funding of research using stem cells derived from the embryos. The case is called Mary Scott Doe v. Obama. This ruling does not bear on Shirley v. Sebelius which is being heard in the District of Columbia.

The U.S. Court of Appeals for the Fourth Circuit held that plaintiffs--Mary Scott Doe, a frozen human embryo--did not have standing to assert constitutional and statutory rights. The Court also ruled that other plaintiffs--people who adopt children from embryos donated for adoption--could not prove that all frozen embryos in the U.S. would be harmed by embryonic stem cell research.

The Court cited judicial restraint for the basis for their decision. The Court stated that there was no standing, because there was no injury-in-fact: "We cannot identify a particularized harm because the complaint does not identify any of the named plaintiff's particularized characteristics. Instead, it leaves us only with questions such as whether the embryo will ever be used for research and whether that research will be funded by the NIH." The Supreme Court has made it clear that named plaintiffs who represent a class must show that they were personally injured, not that injury was suffered by other, unidentified members of the class to which they belong.

The Court also held that plaintiffs could show causation, because they could not connect any harm to embryos to federally-funded research: "Where government policy not only allows the biological parents to choose what to do with their embryos, but also safeguards the independence of their decision with strict conditions, the connection between injury and policy is a 'purely speculative' one."

The Court narrowed its holding further stating: "A complaint that provided more concrete information about the identity of the named plaintiff embryo or the plaintiff parents' plans for adoption would at least address more directly what the Supreme Court has identified as serious constitutional concerns." This undoubtedly leaves the door open for future, more particularized complaints. For additional information about the stem cell research debate, see our blogs here (December 15, 2010), here (December 1, 2010), here (September 13, 2010), and here (August 27, 2010).

by Brian Malkin

On February 2, FDA issued a new draft guidance titled: "Target Animal Safety and Effectiveness Protocol Development and Submission". FDA issued the guidance to help sponsors prepare protocols for review by the Center for Veterinary Medicine ("CVM"), Office of New Animal Drug Evaluation (ONADE). This guidance, which was announced in a Federal Register Notice on February 3, follows a call for sponsors to obtain approvals for unapproved animal drugs that are illegally marketed, which we reported here.

CVM does not require sponsors to submit protocols for approval prior to conducting studies to support substantial evidence of effectiveness or target animal safety. CVM encourages, however, sponsors to have frequent and early contact with CVM through formal meetings and informal communication to ensure study protocols are useful to support new animal drug product approvals.

The guidance explains procedures for submitting presubmission conferences, protocol development meetings, and provides a list of other FDA guidances to consult for developing a protocol. FDA proposes a 50-day review cycle for each protocol, which may include minor amendments along the way, that concludes with concurrence, nonconcurrence, or the need for an End-of-Review Amendment to complete review of the protocol. While comments to guidances may be submitted at any time, FDA requests comments by April 19, which is when FDA expects to begin drafting the final version.

by Mark P. Walters

The U.S. Department of Agriculture ("USDA") has authorized the planting of genetically- modified ("GM"), Roundup Ready® alfalfa. Roundup Ready® Alfalfa is resistant to glyphosate-based herbicides such as Monsanto's Roundup® herbicide. In reaching its decision to permit free, unregulated planting of the biotech crop, USDA abandoned an earlier proposal which would have placed certain restrictions on where and how the crop can be grown. Biotech opponents and organic farmers were unhappy with the decision and vowed in a New York Times article by Paul Voosen that they were "going back to court."

The USDA's decision comes just in time for spring planting and just after the completion of an environmental impact statement in which USDA determined that Roundup Ready® Alfalfa does not pose a plant pest risk.

Biotech supporters say the product offers farmers more weed control options and that safeguards are in place to protect all interests, including those of seed producers and exporters whose customers may be biotech-sensitive. Opponents of biotech crops cite risks of cross pollination with non-GM alfalfa and the potential loss or reduced availability of viable germplasm for non-GM seed, which would impact organic farmers.

PIVDisputes2011

Frommer Lawrence & Haug will co-chair and co-sponsor the Fifth Anniversary Paragraph IV Disputes Conference in New York on May 2-4. FLH Managing Partner Edgar H. Haug will Co-Chair the Conference. Partner Brian J. Malkin will speak on "Exploring Patent Term Adjustment and Patent Term Extensions and Understanding their Applicability to Drugs and Biologics" in the Pre-Conference Workshop on May 2, and FLH will sponsor the Pre-Registration and Welcoming Cocktail Reception. Partner Charles J. Raubicheck is part of a panel on "Mastering Regulatory Maneuvers Essential to Paragraph IV Litigation"

The original ACI Paragraph IV Disputes Conference was co-designed by FLH Partner Barry S. White, who has previously co-chaired the first four Paragraph IV Disputes conferences. This year, FLH Managing Partner Edgar H. Haug builds upon Mr. White's leadership. ACI's faculty includes counsel from both branded and generic companies, renowned federal jurists, and a key official from the Federal Trade Commission. For more information and to register, click here. FDA Lawyers Blog readers can obtain a $200 discount with the code FDALWY.

by Andrew M. Nason

On January 25, Sens. Patrick Leahy (D-Vt.), Orrin Hatch (R-Utah), and Chuck Grassley (R-Iowa) introduced the Patent Reform Act of 2011. This year's version of patent reform legislation incorporates compromises reached in March 2010 (the Managers' Amendment to S. 515) into previous versions of the patent reform bill. When introducing the legislation, Sen. Leahy identified three primary goals the legislation aims to accomplish: (1) transition to a first-to-file system (in order to harmonize the U.S. patent system with those of other countries), (2) improve patent quality, and (3) provide more certainty in patent litigation. Notably, the legislation would allow third parties to submit and explain prior art and other pertinent information concerning claim construction for the examiner's consideration, and it would provide alternatives to litigation for parties seeking to challenge the validity of an issued patent. The legislation would also add a procedure for determining damages awards in patent cases, giving the district court a "gate keeping" role to ensure that juries consider only methodologies and factors relevant to the damages determination, and which have a legally sufficient evidentiary basis. Additionally, the Bill would codify the "objective recklessness" standard of In re Seagate Tech, LLC, 447 F.3d 1360 (Fed. Cir. 2007), for determining willful infringement.

The Biotechnology Industry Organization (BIO), which represents over 1,100 biotechnology companies, academic institutions, state biotechnology centers and related organizations in the United States as well as 30 other nations, supports the legislation. BIO "believe[s] the Patent Reform Act of 2011 will help strengthen and improve our nation's patent system for all users while preserving the incentives necessary to spur the creation of high-wage, high-value jobs and sustain America's global leadership in innovation . . . . The [Act] would improve the patent system in ways that would benefit all sectors of the U.S. Economy by enhancing patent quality and improving the efficiency, objectivity, predictability, and transparency of the patent system."

Other groups, however, have not treated the Bill as kindly. In a letter obtained by National Journal Daily on February 1, a group of more than 20 conservative organizations and activists urged congressional leaders to prevent passage of the legislation. According to the letter's authors, the suggested reforms would hamper U.S. competitiveness by removing incentives for innovation and commercialization of new products and processes. The Bill's opponents claim the proposed reforms only benefit large, established corporate market players at the expense of U.S. economic growth, which they attribute to start-up companies and independent inventors. They fear that larger information technology companies only want current law rewritten to make post-grant challenges to patents easier and more frequent in order to solidify their own market positions.

Disentangling Biobetters under the Biologics Price Competition and Innovation Act of 2009

Brian J. Malkin and Andrew S. Wasson wrote an article appearing in the January/February 2011 Food Drug and Law Institute Update titled "Disentangling Biobetters under the Biologics Price Competition and Innovation Act of 2009." The article tests the hypothesis whether the Biologics Price Competition and Innovation Act of 2009 will govern biobetters and provides a rigorous analysis of biosimilarity. You can view this and other articles written by the FDA Lawyers Blog's Contributors in the Articles tab. You can learn more about biobetters and biosimilars in the Biosimilars Resources tab for FDA Lawyers Blog.

by Richard F. Kurz

Pfizer, Inc. was dealt another blow in the ongoing In re Neurontin Marketing and Sales Practices Litigation battle. On January 27, U.S. District Court Judge Patti B. Saris (D. Mass.) awarded Plaintiffs Kaiser Foundation Health Plan and Kaiser Foundation Hospitals treble damages of $142 million under the federal RICO statute ("Racketeer Influenced and Corrupt Organizations Act"). The award could have been higher--Judge Saris denied an additional, estimated $76 million prejudgment interest award requested by the Plaintiffs. Pfizer intends to appeal the decision, according to a spokesperson quoted in a Bloomberg article by Jef Feeley and Janelle Lawrence.

This case concerns the marketing practices used to help make Neurontin® (gabapentin) "one of the top selling drugs in the world." The Court detailed its findings in a November 3, 2010, 146-page document. Significantly, the court found that Neurontin®'s success resulted from "a nationwide effort to unlawfully market this drug for off-label uses for which there was little or no scientific evidence of efficacy." Such marketing is prohibited under the Food, Drug and Cosmetic Act.

Specifically, after a five-week trial, a federal jury decided that Pfizer engaged in mail and wire fraud by marketing Neurontin® for off-label treatment of bipolar disorder, neuropathic pain, and migraines, as well as at doses greater than 1800 mg/day. This marketing included showcasing Neurontin®'s efficacy in publications, while suppressing negative results from Pfizer-sponsored clinical trials. Neurontin® is presently indicated only for postherpetic neuralgia (a nerve pain caused by a type of herpes virus) and epilepsy.

Notably, this action is related to a larger, multi-district litigation against Pfizer that consolidates Neurontin®-related civil lawsuits brought nationwide. A group of cases includes products liability actions claiming that Neurontin® caused someone to commit or attempt to commit suicide, and another group of cases related to Neurontin® sales and marketing.

by Elizabeth Murphy

On January 21, FDA announced the withdrawal of a draft guidance document released in August 2010, titled "Draft Guidance for Industry: Questions and Answers Regarding Implementation of the Menu Labeling Provisions of Section 4205 of the Patient Protection and Affordable Care Act of 2010." As FDA Lawyers Blog reported previously, this guidance document was directed to nutritional labeling requirements for menus at restaurants and "similar retail food establishments" (or "SRFEs") with 20 or more locations. FDA had initially hoped to issue final guidance and enforcement policies by December 2010. Based at least in part by comments received since publication of the draft guidance back in August, however, FDA has indicated a new deadline of March 23, 2011 for the issue of proposed regulations. FDA intends that this revised timeline will "most rapidly lead to full and consistent availability of the newly required nutrition information for consumers."