FDA Lawyers Blog

On April 1, FDA issued a Federal Register Notice announcing a new draft biosimilars guidance, "Formal Meetings Between the FDA and Biosimilar Biological Product Sponsors or Applicants". This is the latest in FDA's new biosimilar guidances for 2013, which FDA has announced in earlier meetings this year would be coming to help spur the filing of a biosimilars application, which FDA has called 351(k) applications based on the section in the Public Health Service Act ("PHS Act"). As of a few weeks ago at the Massachusetts Biotechnology Association's ("MassBio's") Annual Meeting, which we blogged on here, FDA's Commissioner, Margaret A. Hamburg, M.D., continued to report that FDA has not received a single 351(k) application to date.

Written by Brian J. Malkin

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The Guidance focuses on formal meetings for 351(k) applications and the associated requirements or performance goals from the Biosimilar User Fee Act of 2012 ("BsUFA"), which was enacted as part of the Food and Drug Administration Safety and Innovation Act ("FDASIA"). In particular, the Guidance discusses the principles of good meeting management practices ("GMMPs") and describes standardized procedures for requesting, preparing, scheduling, conducting, and documenting such formal meetings.

On March 27, FLH attorneys Brian Malkin and Christopher Gosselin attended the International Trade Commission ("ITC") Trial Lawyer's Association ("ITCTLA") luncheon with administrative law judge ("ALJ") Thomas B. Pender. Judge Pender joined the ITC in October, 2011, and is one of six ALJs at the Commission.

Judge Pender arrived at the luncheon with a number of themes that he wanted to discuss. Chief among them is a concern shared by many other ALJs and district court judges about the scope of electronic discovery in today's litigation. He urged the practitioners in the room not to lose control of the paper, and to reign in the costs and scope of electronic discovery. In Pender's experience, less than 1% of all discovery becomes an exhibit, and less than 5% of those exhibits are ever argued. In addition to paring back discovery, Pender would like to see fewer patents and patent claims being asserted by complainants. Ultimately, Pender would like to see more efforts taken to reduce the cost of litigation at the ITC, and hopes that more streamlined cases will allow him to finish an Initial Determination in a year or less.

Written by Christopher Gosselin

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Judge Pender also suggested, on a related note, that big firms make an effort to send their associates "to the podium," both to give the associates valuable experience, and to reduce the cost of a trial. In his experience, well-prepared associates perform as well or better than partners who had less time to prepare. Pender cautioned parties to think twice before betting an entire case on one witness, and suggested that secondary witnesses could and should be handled by associates.

On March 25, 2013, the U.S. Supreme Court heard oral argument in the Federal Trade Commission's ("FTC's") case challenging the Hatch-Waxman patent settlements Solvay (now owned by Abbot Laboratories) entered into with Watson Pharmaceuticals, Par Pharmaceutical, and Paddock Laboratories resolving their disputes involving Solvay's testosterone-replacement drug AndroGel®. The so-called reverse-payment settlements at issue in FTC v. Actavis, Inc., Sup. Ct. No. 12-416 ("AndroGel") involved the generic manufacturers' agreements to abandon their patent challenges and delay generic entry for nine years. The settlements also involved Solvay making certain payments to the generic manufacturers in return for backup manufacturing and marketing support. For additional background information, please see some of our more recent blogs here, here, and here.

The issue before the Court is whether reverse-payment settlements are per se lawful unless the underlying patent litigation was a sham or the patent was obtained by fraud (as the Eleventh and other circuits have held), or instead are presumptively anticompetitive and unlawful (as the Third Circuit held in K-Dur).

Written by Justine K. Donahue

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Deputy U.S. Solicitor General Malcolm L. Stewart argued on behalf of the FTC that the Court should adopt a "quick look" rule of reason analysis under the antitrust laws whereby reverse-payment settlements will be presumptively anticompetitive unless defendants can show that the payment from the brand to the generic was for a purpose other than delaying generic entry, or the payment offered some pro-competitive benefit. Notably, this quick look approach was adopted by the Third Circuit in K-Dur. Counsel for the respondent drug companies argued that the Court should adopt the "scope of the patent defense" applied by the Second, Eleventh, and Federal Circuits finding these agreements to be lawful absent sham litigation or fraud in obtaining the patent.

In a surprising turn of events, last week FDA's new Office of Generic Drugs ("OGD") Director Gregory P. Geba, M.D., M.P.H., voluntarily stepped down from his post after only about eight months after being announced as the new Director. Rather than hiring from within, FDA hired Geba from Sanofi US, where he had previously most recently served as Deputy Chief Medical Officer. FDA said then, "He [Geba] joins OGD at an opportune time to lead our expanding generic program into a reorganization of both structure and process to improve coordination, communication, and efficiency, as well as enhance the Office's ability to ensure that all generic drugs--which make up nearly 80 percent of prescriptions filled in the United States--are safe, effective, of high quality, and interchangeable with the brand name drug product/reference listed drug." Around this same time, FDA moved OGD to the same organizational level as the Office of New Drugs ("OND"), called a "Super office," signaling that the two offices now had the same reporting structure directly to the Director of the Center for Drug Evaluation and Research ("CDER"), Janet Woodcock, M.D., rather than a sub-office, as had previously been the case.

According to reports of an e-mail that Geba sent to FDA staff on March 13, Geba cited the movement of OGD's chemistry divisions into a new Office of Pharmaceutical Quality as one of the lead reasons for his resignation, as well as the relocation of his family to the Washington area. Geba reportedly wrote: "As I see it, two of the original reasons I came to [OGD] . . . would be challenged by resources needed for application to other extremely important efforts of the chemistry group in moving to [the Office of Pharmaceutical Quality." The e-mail explained that while Geba generally supported the transfer of the chemistry group to the Office of Pharmaceutical Quality. Geba thought, however, that the move could make it difficult for him to achieve his goals to approve generic versions of inhalers, topical creams, and other complex drugs, as well as addressing the importance of pill size, shape, color, and other characteristics to patients.

Written by Brian J. Malkin

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Geba helped FDA with its initial phases for implementing the Generic Drug User Fee Act ("GDUFA"). According to Geba, since GDUFA, OGD decreased the abbreviated new drug application ("ANDA") backlog by nearly 600 applications and approved nearly 200 ANDAs since October 2012.

On March 14-15, the Massachusetts Biotechnology Council ("MassBio") held its Annual Meeting in Cambridge, Massachusetts. The Meeting also featured a Keynote from FDA Commissioner Margaret A. Hamburg, M.D. (see related blog here). Key themes at the Meeting were the importance of the Cambridge/Boston biotechnology community for advancing new therapies and the unique resources available in the area that have made it an industry leader. Some of the Cambridge/Boston advantages discussed were the intellectual research capital (local universities such as Harvard and Massachusetts Institute of Technology), venture capital, and local biotechnology businesses, such as Biogen Idec and Genzyme, as well as other biotechnology companies that now have offices in the Cambridge/Boston area and are seeking partnerships to develop new products, such as AstraZeneca, Pfizer, Merck, Novo Nordisk, and Sanofi.

On the second day, Hamburg described here "special affection" for the Cambridge/Boston region dating back to her days at Harvard, saying that she hopes D.C. "would be as efficient and congenial as here." Hamburg said that the Cambridge/Boston region is a life sciences enterprise fueled by top notch research and medical care with the top five NIH-funded hospitals and a "biotech supercluster second to none" with "a remarkable 500 biotech and pharma companies here, and some thirty venture capital firms."

Written by Brian J. Malkin

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Hamburg described FDA as striving for true collaboration and regulatory flexibility with industry, including MassBio, and has been hearing that industry wants more clarity, certainty, transparency with decisions. Hamburg said that FDA is trying to have creative approaches--not a one size-fits-all approach. To this end, Hamburg described approaches that FDA has taken with four new products from the Massachusetts area: 1) Inclusig® for two rare forms of leukemia, 2) Juxtapid® (an orphan drug), 3) Linzess® for irritable bowl syndrome, and 4) Kalydeco® for cystic fibrosis. In addition, Hamburg highlighted new provisions in the Food and Drug Administration Safety and Innovation Act ("FDASIA") for expedited approvals, citing 31 breakthrough therapy designation requests, of which 9 have been granted, 10 denied, 11 pending, and 1 withdrawn. To help with more companies taking advantage of this new process, FDA will be publishing a new guidance shortly, Hamburg announced.

On March 14-15, the Massachusetts Biotechnology Council ("MassBio") held its Annual Meeting in Cambridge, Massachusetts. The Meeting featured key topics such as biosimilars and a Keynote from John Crowley, Chairman and CEO of Amicus Therapeutics.

On the first day of the conference, Crowley exemplified many of the speakers' entry in biotechnology, which originated with a family member or friend with a disease requiring development of a biotechnology product. For Crowley, it was his two children Megan and Patrick, were diagnosed with a severe neuromuscular disorder, Glycogen storage disease type II, known as Pompe's disease. Rather that sitting still to wait for a cure, Crowley became involved in the process, first moving to Princeton, New Jersey, to be close to doctors specializing in the disease and leaving his job with Bristol-Myers Squibb. He later took a position as CEO of Novazyme Pharmaceuticals, a biotechnology research company located in Oklahoma City founded by Dr. William Canfield, which was conducting research on a new experimental treatment for the disease. Novazyme was acquired by Genzyme Corporation, which was then the world's third largest biotechnology company. Crowley was put in charge of Genzyme's global Pompe program, becoming the largest research and development effort in the company's history.

Written by Brian J. Malkin

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Through these efforts, an experimental enzyme replacement therapy was developed, and Megan and Patrick Crowley received the therapy, which Crowley credits with saving his children's lives. Crowley went on to become President and CEO of Orexigen Therapeutics and was named the President and CEO of Amicus Therapeutics, based in Cranbury, New Jersey, which he helped take public in 2007. Crowley's efforts were documented in a Wall Street Journal article and other publications, which ultimately resulted in Harrison Ford working to bring the story to life in a major motion picture, Extraordinary Measures.

Written by Dario A. Machleidt

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On January 28, 2013, consumer-advocacy group Public Citizen filed a letter "in response" for FDA to reconsider its August 8, 2012 denial of the group's petition that asked FDA to withdraw its approval for a medical device directed to stent technology. Public Citizen's original petition urged the withdrawal of approval for and recall of Stryker Corporation's ("Stryker's") Wingspan Stent System with Gateway PTA Balloon Catheter ("Wingspan Stent"), which is used to treat narrowing of the blood vessels in the brain.

In its January 28 letter, Public Citizen claimed that FDA denied the petition based on flawed reasoning. Specifically, Public Citizen argued that FDA's decision minimized the importance of crucial scientific evidence indicating that the Wingspan Stent is ineffective and, furthermore, that it is more harmful to patients experiencing intracranial narrowing of the blood vessels when compared to alternative forms of treatment. Public Citizen also criticized FDA's attempt at comprise by narrowing the proposed indication of the stent in response to the scientific data outlined in the petition. Public Citizen argued that such attempts fell far short of being sufficient to ensure the safety of patients that might consider using Stryker's medical device.

The Wingspan Stent is a class III medical device that comprises a stent with a balloon catheter and, until recently, was indicated for use "in improving cerebral artery lumen diameter in patients with intracranial atherosclerotic disease, refractory to medical therapy, in intracranial vessels with ≥ 50% stenosis [(a narrowing of the blood vessels that supply blood to the brain)] that are accessible to the system." In simple terms, the device uses a self-expanding tube that is inserted into a blocked artery in the brain with the "goal of increasing blood flow and preventing strokes in patients who have experienced repeat strokes, even after taking medication to prevent blood clotting."

Eric "Rick" Blumberg, an attorney with FDA for over 40 years, passed away unexpectedly yesterday. His noteworthy achievements include winning the Park case, which reaffirmed the strict liability rule in FDA criminal proceedings, and implementing the doctrine of disgorgement in FDA enforcement actions. A graduate of Washington & Lee and Georgetown Law, he will truly be missed by the FDA bar.

Written by Charles J. Raubicheck

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The Supreme Court has another chance to clarify the scope of the safe-harbor provisions of 35 U.S.C. § 271(e)(1). Momenta Pharmaceuticals, Inc. and Sandoz Inc. petitioned the Supreme Court to review Momenta Pharmaceuticals, Inc. v. Amphastar Pharmaceuticals, Inc.. In that case, the Federal Circuit held that 35 U.S.C. § 271(e)(1) protected post-approval studies performed for FDA. Momenta's request comes roughly one month after the Supreme Court declined to grant cert in Classen Immunotherapies, Inc. v. Biogen Idec, another Federal Circuit case involving the scope of 271(e)(1) (blogged on here).

Momenta identifies the issue for the Supreme Court as:

Whether the use of a patented invention in the course of post-approval manufacture of a drug for commercial sale, where the FDA requires that a record of that manufacturing activity be maintained, is exempt from liability for patent infringement under Section 271(e)(1) as "solely for uses reasonably related to the development and submission of information under a Federal law which regulations the manufacture, use, or sale of drugs.

Written by Scot B. Pittman

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The generic-drug company seeks Supreme Court intervention to remedy what it views as inconsistent and incorrect Federal Circuit law. The safe harbor states that it is not an act of infringement to make, use, offer to sell, or sell a patented invention solely for uses reasonably related to the development and submission of information under [federal drug laws]. 21 U.S.C. § 271(e)(1). In Classen, a divided Federal Circuit panel interpreted the provision to be limited to "activities conducted to obtain pre-marketing approval of generic counterparts of patented inventions, before patent expiration." Roughly one year later, another divided Federal Circuit panel, in Momenta, held that "the requirement to maintain records for FDA inspection satisfies the requirement that the uses be reasonably related to the development and submission of information to FDA.

On March 5, FDA issued a new draft guidance, "Types of Communication During the Review of Medical Device Submissions." During the development of the various medical device user fee amendments ("MDUFA"), the discussion of improving communications between device applicants and FDA was suggested, described as an Interactive Review. The collection of additional funds from MDUFA-related activities will enable FDA to improve the device review process and help meet certain performance goals incorporated into MDUFA. Some of the suggested communications included Acceptance Review, Substantive Interactions, Interactive Review, and, where applicable, Missed MDUFA Goals.

The purpose of Acceptance Review communications are to: (1) identify the lead reviewer or Regulatory Project Manager assigned to the submission and (2) confirm acceptance of the submission or notify the submitter that the submission was not accepted based upon the review of objective acceptance criteria. FDA aims to make these communications within 15 days of receipt of a 510(k), original premarket approval application ("PMA"), or a Panel-Track PMA Supplement, with such confirmation by fax, e-mail, or other written communication.

Written by Brian J. Malkin

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Substantive Interactions tell applicants that FDA either: (1) intends to continue working with the applicant to resolve any outstanding deficiencies (no hold), or (2) FDA has identified deficiencies sufficient to place the submission on hold. Substantive Interactions should occur following acceptance of the submission and only after FDA has performed a complete review with targets of within 60 days of receipt of a complete 510(k) or within 90 days of the filing date of an original PMA, Panel-Track PMA Supplement, or 180-Day PMA Supplement.

Written by Rachael P. McClure

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With the $85 billion spending cuts now in effect, it is time for FDA and other agencies to adapt. The 2013 impact will be condensed into the next seven months because the federal fiscal year ends on October 1. While few details have been made available, FDA Commissioner Margaret A. Hamburg, M.D. said in an interview on Thursday that she did not anticipate FDA having to furlough workers and emphasized that the majority of the effects would not be felt in the short term. However, Hamburg estimated that the cuts will result in more than 2,000 fewer food safety inspections: "[C]learly we will be able to provide less of the oversight functions and we won't be able to broaden our reach to new facilities either, so inevitably that increases risk." FDA may renew efforts to implement a user fee program for the food industry to offset this hit.

President Barack Obama has vowed to continue to work with Congress to reach a compromise that would replace the cuts with a more balanced budget plan. Meanwhile, the House Appropriations Committee introduced a bill yesterday that would fund the government with $982 billion through the end of the fiscal year, assuming the sequester cuts would remain in effect. While largely focused on the Department of Defense ($518 billion) and military construction and Veterans Affairs ($71.9 billion), the general provisions maintain the funding level of the Agriculture, Rural Development, Food and Drug Administration, and Related Agencies Appropriations Act, 2012. The bill is scheduled to reach the House floor tomorrow.

Absent an agreement in today's Senate votes on dueling legislative proposals to prevent the budget "sequester," automatic wholesale spending cuts will likely take effect tomorrow evening in the form of a 5% hit for all government agencies. This will amount to $85 billion (2.4% of the federal budget) in total. The cuts are a result of a 2011 law mandating that, if Democrats and Republicans should be unable to agree on a plan to reach the goal of $4 trillion in deficit reduction, then over a trillion dollars of arbitrary cuts would start to take effect this year. The draconian nature of the law was an intentional effort to force the parties to reach some other compromise.

A failure to achieve that goal may now have serious consequences, in particular for the healthcare industry. Estimated cuts for this fiscal year include $210 million to FDA, $1.6 billion to the National Institutes of Health ("NIH"), and $11 billion to Medicare. While the so-called "mandatory" programs (Medicaid, the Children's Health Insurance Program, and Social Security) are exempt, the remaining reductions have given the industry more than enough to worry about. According to Bill Hall, spokesman for the Department of Human Health and Services, "It will affect all disease areas, all research areas. Because it is across the board and deep down in every single institute, it would affect virtually everything."

Written by Rachael P. McClure

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More specifically, hospitals and doctors anticipate a 2% cut in Medicare reimbursement fees and, by some estimates, up to 200,000 job losses; the pharmaceutical industry expects a substantial increase in drug and medical device approval delays from FDA; and research institutes will undoubtedly see the effects of the NIH cuts. Francis Collins, director of NIH called the sequester "sand in the engine" that will force NIH to reject 1,000 promising new research proposals. As a result, he continued, "Medical research in America will be slowed by this, advances that could have happened sooner will happen later or perhaps not at all..." The pharmaceutical industry may also see effects of research program cuts to the extent of NIH-industry collaboration.

Written by Brian J. Malkin

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The last day of the Generic Pharmaceutical Association ("GPhA") 2013 Annual Meeting also featured an FDA Keynote Address by FDA Commissioner Margaret A. Hamburg, M.D. For a summary of public sessions from Day Two, please see the previous blog here; a summary of the CEOs Unplugged session may be found here.

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Following the CEOs Unplugged session on day three, Hamburg delivered her Keynote Address. Hamburg said that GPhA was one of the few organizations that she has chosen to address each year since becoming Commissioner, "because of the dynamic character of this group, your prominent role in the nation's health care system and the importance of the work you do." Celebrating GDUFA and the FDA Safety and Innovation Act ("FDASIA"), Hamburg emphasized that FDA is making "quality one of the highest priorities this year," hoping that GPhA's members do the same. Despite generic drug companies providing 85 percent of all prescriptions filled, some studies have suggested that many physicians still have "negative perceptions about the quality of generic medicines," which Hamburg said was "troublesome - and assuredly not fair."

Hamburg reported "impressive strides in implementing GDUFA," explaining that FDA got the word out of new requirements and fees early, resulting in the collection of almost $125 million in fiscal year 2013 user fees to help brining in staff and other resources to help reduce the backlog of ANDAs above 2,500 applications with median review times at about 31 months. FDA has assembled a list of about 2,000 facilities supplying generic drugs to the U.S. following self-identification procedures.

Written by Brian J. Malkin

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The last day of the Generic Pharmaceutical Association ("GPhA") 2013 Annual Meeting featured a program known as "CEOs Unplugged" and an FDA Keynote Address by FDA Commissioner Margaret A. Hamburg, M.D. For a summary of public sessions from Day Two, see the previous blog here. This blog focuses on the CEOs Unplugged session. A subsequent blog will cover FDA's Keynote Address.

The CEOs selected for this year's program included Donald DeGolyer, President, Sandoz, Inc., Tony Mauro, President, Mylan, North America, Thomas Moore, President, Hospira USA, Allan Oberman, President and CEO, Teva Americas Generics, and Siggi Olafsson, President, Actavis Pharma.

Perhaps Oberman summed up the overall themes best when he acknowledged that the lines between innovator and generics are beginning to blur, where generic medicines are becoming more complex, and generic manufacturers are increasingly seeking a niche to compete in. The CEOs noted that none of the same CEOs were on the stage five years ago, which signals just how much the key players and CEOs have been changing. Other comments Oberman made included: (1) he hoped the Generic Drug User Fee Act ("GDUFA") approval and efficacy measures would be used effectively and manufacturing sites outside the U.S. would be under similar scrutiny as in the U.S., (2) no one is really planning for shortages, but it is important to have effective communication to prevent them in particular with FDA, (3) industry needs to stop "fear mongering" to figure out when biosimilars will be approved or interchangeable--some people will take biosimilars and others will not, just as with generic drugs, (4) more mergers in the generic pharmaceutical industry should be expected, especially in emerging markets, (5) generic pharmaceuticals should be more available in the eastern part of the world where access to medicine may still be restricted, which provides more growth opportunities, and (6) traditional generic manufacturers should consider either developing new molecular entities or combining older generics in ways to improve convenience, safety, or effectiveness.

Written by Brian J. Malkin

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On February 20-22, 2013, the Generic Pharmaceutical Association ("GPhA") held its 2013 Annual Meeting attracting over 600 attendees to see how the nation's health and regulatory issues will impact the generic industry and consumers who use generic medicines. While some events are for GPhA members only, a majority of the events are open to all attendees and were held in a single room or exhibit hall. Most of the main events were held in a slickly-decorated room filled with stars, comets, and planets.

While the Meeting covered a lot of territory, recurrent themes appeared to emphasize that the generic industry has come of age, where it joins its big-pharma brothers in having an office on par level with the Office of New Drugs ("OND") in FDA's Center for Drug Evaluation and Research ("CDER") and now pays user fees to speed up generic drug approvals. GPhA's members announced that they are ready to develop high quality generic versions of specialty pharmaceuticals and biologics, some of which may require the expenditure of hundreds or more millions of dollars to develop, obtain approval for, and market. At the same time, GPhA appears to hold onto the notions that that they can continue to settle cases with reverse payments that the Federal Trade Commission ("FTC") views as so-called "pay-for-delay" settlements that are presumptively anticompetitive. GPhA also believes that manufacturers should be allowed to sell generic versions of products with the same labeling as the innovator, when the innovator or generic companies that manufacture and sell the product are aware of safety information not presently included in the FDA-approved labeling.

Kicking off the meeting with a "State of the Association", GPhA President and CEO Ralph G. Neas described generic drugs as the "backbone of the pharmaceutical industry." Neas expressed the Association's confidence that FDA will "come through" and help the industry understand what will be expected of it to develop biosimilars and interchangeable biosimilars, which are the future to save lives and money.