FDA Lawyers Blog

FDA Lawyers Blog is pleased to announce that FLH Partner Brian J. Malkin was quoted in an FDAnews article by David Pittman commenting on the FDA e-mail monitoring suit concerning several FDA whistleblowers in the Center for Devices and Radiological Health.

The article is printed below, but you must have a subscription to FDAnews to Access this article and other content on FDAnews:

FDA Email Monitoring Suit May Chill Whistleblowing on Safety Concerns

The FDA's alleged monitoring of the personal emails of employees who voiced product safety concerns to Congress could dissuade other staffers from airing grievances, industry experts tell DID.

Several FDA staffers are suing the agency, claiming it monitored personal email accounts from the government computers of six FDA scientists and doctors. These employees had contacted congressional staff to draft whistleblower complaints about what they believed were unsafe medical devices that gained approval, according to a lawsuit filed last week in Washington, D.C. federal court. The staffers were harassed and eventually fired from their positions in the Center for Devices and Radiological Health, according to the suit.

If the allegations are true, "this is the kind of retaliation that will intimidate other scientists from stepping forward when they are aware of wrongdoing," Joe Newman, spokesman for FDA watchdog Project on Government Oversight, told DID. "One has to wonder why the FDA seems more concerned about punishing whistleblowers than it is about getting to the bottom of their grievances."

The HHS Office of Inspector General found no criminal conduct and said the staffers had a right to communicate with Congress and journalists.

The FDA's alleged actions, if true, would place employees in a difficult situation, experts said. They would either need to leave the agency to voice their concerns or risk seeing complaints go unanswered if speaking through authorized channels.

The FDA wants its official communications to Congress to go through the agency's legislative office, rather than individuals.

Brian Malkin, attorney with Frommer Lawrence & Haug and a former FDA staffer, suggests the agency clarify what communications its employees can have with legislative staff and other outsiders.

And it should establish criteria for what information can and can't be shared with outsiders, Richard Samp, chief counsel at the Washington Legal Foundation, told DID. Whistleblowers are supposed to expose corruption, not simply publicize the decisions they disagree with, he said.

The FDA does not comment on pending legal actions, an agency spokeswoman told DID.

View the lawsuit at www.fdanews.com/ext/files/CDRH_lawsuit.pdf. -- David Pittman

American Conference Institute presents: The Comprehensive Guide to PATENT REFORM For Life Sciences Companies: The critical industry forum on the Leahy-Smith America Invents Act
*Jan. 31-Feb. 1, 2012* Flatotel * New York, NY

Attend and hear USPTO Insights and Guidance on the AIA:

Teresa Stanek Rea
Deputy Under Secretary of Commerce for Intellectual Property and Deputy
Director, USPTO

Janet Gongola
Patent Reform Coordinator, USPTO

Keynote Address:
Robert L. Stoll
Former Commissioner for Patents, USPTO

With the historic passing of The America Invents Act, H.R. 1249, the United States is now facing the most significant patent reform in more than 60 years. Patent reform is now a reality. With countless complicated nuances throughout the statute and the unknown implications of these provisions looming, patent practitioners have been left with a multitude of questions regarding the overwhelming potential ramifications of the AIA on their patent practices. One thing is clear - with so much at stake for life sciences companies, you must plan now for the changes both in effect already and on the horizon in order to protect and defend invaluable intellectual property.

The expert faculty will discuss answers to the most pressing questions facing patent practitioners resulting from the AIA including:

• What does "first to file" actually mean under the AIA requirements? Which system can you or should file under - the current first to invent or the new first to file (or both)? And how do you avoid first-to-file bubble filings before 3/15/2013?
• When can on-sale and public use activity be considered prior art? Has secret §102(f) prior art been eliminated?
• Do you need to include best mode in the application or not and what happens if you don't? Is best mode completely toothless now? How will examiners be able to address the best mode issue?
• What will be required in the PGR process? What type of discovery? Expert witnesses? How do the estoppel provisions alter your analysis of whether to engage in the PGR system?
• What estoppel provisions are associated with IPRs and how are these different from the inter partes reexamination provisions? When do you file a 3rd party parallel IPR?
• What does the prohibition to patenting human organisms actually mean for the life sciences industry?
• What qualifies as a micro-entity and how do micro entities take advantage of the new fee reduction provisions available to them? Do you need to file an IDS with prioritized examination applications?

For more Information, please visit our website: http://www.americanconference.com/patentreform

by Brian Malkin

On January 26, FDA's Acting Chief Counsel, Elizabeth H. Dickinson, Esq., and FDA's Deputy Center Director for Policy, Center for Devices and Radiological Health ("CDRH"), Nancy K. Stade, Esq., spoke at the Annual Meeting of the Food, Drug and Cosmetic Law Section of the New York State Bar Association. Dickinson provided an overview of the year's hot legal issues and Stade offered her views on FDA's efforts for improving its medical review process and plans for the future.

Stade spoke first in a spirited debate between former FDA and current consultant Philip J. Phillips, Esq., President, Phillips Consulting Group, LLC, Professor Ralph F. Hall, Professor of Practice, University of Minnesota Law School, and Partner, Lauren R. Silvis, Esq., Sidley Austin LLP. Section 513 of the Food, Drug, and Cosmetic Act ("FD&C Act") mandates that, prior to marketing, FDA must classify all medical devices into one of three classes depending on the intended use, indications for use, and level of control necessary to ensure the safety and effectiveness of the device. Class I requires the least control, followed by class II, and class III requires the most control. Section 513(i) of the FD&C Act essentially states that if a new device is substantially equivalent to an already-marketed device or "predicate" device, the new device is given the same classification as the device already in the market and may be submitted as a "510(k)" submission, which is based on section 510(k) of the FD&C Act. If the new device is not substantially equivalent to any such device, the new device is placed in class III and requires a premarket approval application ("PMA") under Section 515 of the FD&C Act.

Over the years, the 510(k) process has become the most common and controversial pathway for bringing medical devices to market. FDA's definition of medical device includes products ranging from simple tongue depressors to pacemakers to laser surgical devices. Under the current 510(k) process, device manufacturers must notify FDA of their intent to market a medical device at least 90 days prior to launch. If FDA determines that the device is substantially equivalent to an existing 510(k) cleared device or other device that was on the market when the Medical Device Amendments were enacted in 1976, then it may proceed to market. If not, it must undergo pre-market approval as a premarket approval application ("PMA").

by Brian Malkin

On January 23, The Wall Street Journal published a debate whether innovation would be sparked in the pharmaceutical industry by a further form of patent term extension. While it is clear that patent protection is key for innovators to protect their blockbuster products from generic competition, it is not so clear whether extending patent protection for this class of products drives or hinders innovation.

Josh Bloom, Director of Chemical and Pharmaceutical Sciences at the American Council on Science and Health, a health-care education and advocacy group based in New York, took the position that the pharmaceutical industry needs more and longer patent term protection to help support basic research and development that produces needed breakthrough products. According to Bloom, there are "far fewer" scientists engaged in pharmaceutical research than there were 10 years ago, in part because longer development times have translated to less time left on patents following new product approvals. Bloom describes this as an approaching "financial crisis" or "patent cliff" where a series of patents will soon expire for some of the most profitable innovator drugs, translating to lost profits on branded products approaching an estimated $160 billion in 2015.

Unlike the "steady stream of blockbuster drugs" in the 1990s, Bloom observes, newer products that treat more complicated diseases have required more clinical studies with more subjects, adding costs and extending development times. Extending the patents on current blockbusters would postpone the patent cliff and provide additional research time for more innovative products, Bloom speculates. Generic drugs, Bloom says, "contribute nothing to innovation. . . . [y]et they take up to 90% of sales away from the comparable brand-name drugs." But Bloom wants to discourage pharmaceutical companies from merely developing line extensions for current therapies and would propose that new products receive five year extensions, whereas patents for line extensions would only receive three years of extension.

by Brian Malkin

On January 18, FDA announced in the Federal Register the availability of a new final guidance, "Preparation of IDEs and INDs for Products Intended to Repair or Replace Knee Cartilage." Dated December 2011, the Guidance finalizes a draft guidance of the same title dated July 2007 and is a joint collaboration of the Center for Biologics Evaluation and Research ("CBER") and the Center for Devices and Radiological Health ("CDRH"), reflecting that products in this category typically are a biologic, medical device, or combination of the two. The guidance does not apply to prostheses such as unicondylar or total knee implants, or meniscus replacement products, nor does it apply to human cells, tissues, and cellular products and tissue-based products regulated solely under Section 361 of the Public Health Service.

According to FDA, it received "numerous" comments on its 2007 draft guidance, resulting in new sections and clinical study schedules with elaborations on nonclinical data considerations, as well as input from a public meeting of the Cellular, Tissue, and Gene Therapy Advisory Committee meeting on May 15, 2009.

The Guidance notes that FDA believes investigational devices for articular cartilage repair or replacement are significant risk devices requiring the submission of an investigational device exemption or investigational new drug exemption meeting there requisite requirements prior to initiating human research. In particular, FDA notes that approval of an Institutional Review Board ("IRB") alone is not sufficient to commence a clinical study for these types of products.

by Kyle Deighan

On January 17, Representative Mary Bono Mack (R-Cal.) sent a letter to FDA Commissioner Margaret A. Hamburg, M.D., criticizing FDA for its lack of oversight at a Novartis facility in Nebraska. Concerned about numerous quality control problems at the facility over the past few years, she wrote that FDA's "lack of action has resulted in the potential for consumers to unknowingly use highly addictive and, when not taken appropriately, dangerous prescription painkillers." Rep. Bono Mack's concern stemmed from a series of production line mix-ups at the facility that could have resulted in painkillers inadvertently being mixed into bottles with other drugs.

According to the letter, the Novartis facility has been the site of a myriad of regulatory issues, including "12 citations for quality control problems, 166 complaints of mixed pills in bottles since 2009, 223 customer complaints received by the manufacturing facility, and most recently, persistent problems with packaging." Despite the fact that problems at the facility have been ongoing for several years, it took until mid-December for the facility to voluntarily close. Novartis then waited several weeks before issuing a recall of the affected drugs. Rep. Bono Mack faulted FDA for not administering recalls of all drugs that may have been affected, including prescription painkillers, on the same day the manufacturing facility was closed. She wrote:

I am outraged at the lack of leadership shown by FDA to guarantee the safety of patients across the country, and it perplexes me that inspectors continued citing problems with the facility without holding Novartis accountable. If FDA had taken a more proactive, consistent role in the ongoing inspections, the recall by Novartis could have been avoided and consumers would not be at risk of accidentally taking prescription painkillers in place of over-the-counter drugs such as Gas-X.

by Scot B. Pittman

FDA and medical device industry missed this week's deadline for submitting a medical device user fee agreement to Congress. An agreement is necessary to reauthorize user fees for fiscal years 2013 through 2017. User fee programs provide funding FDA can use to conduct its product reviews and approvals. In exchange for the money, FDA agrees to certain performances goals, such as completing a certain percentage of new applications within a certain time period.

As FDA Lawyers Blog reported here, FDA was able to submit proposals for prescription drug, generic drug, and biosimilar user fees on time, but the agency and the medical device industry are deadlocked over how to finance the five-year plan. According to meeting minutes FDA released earlier this month, the sides remain hundreds of millions of dollars apart. As of December 6, 2011, the medical device industry was proposing $447 million over five years with a possible additional $38 million over the final three if certain goals were met, but FDA was asking for between $730 and $805 million. FDA's proposal was down from a high of $1.15 billion, and the industry's offer increased from an earlier $401 million proposal, but it is clear that the parties have a long way to go. We will have to wait for the minutes of the December 13 and January 5 meetings to be posted to see if the two have narrowed the gap.

While the sides are struggling to agree on the fees, they appear to have reached a consensus on the improvements the 2012 reauthorization should include. Significant performance commitments outlined in the draft Commitment Letter are as follows:

• A single review goal for 510(k)s and PMAs based on total review time.
• A single-tiered system for 510(k)s and PMAs to replace the current two-tiered goal system.
• FDA will try and schedule pre-submission meetings or teleconferences within a certain time period after receiving a pre-submission request. Meeting minutes will be finalized within two months of the meeting.
• A revised acceptance criteria checklist aimed at rejecting sub-par submissions.
• Time goals for interacting with a sponsor after a complete review of a submission.
• Better and more frequent guidance documents.

by Brian Malkin

On December 23, FDA launched its newest official blog called "FDA Voice". FDA Voice's first blog entry, authored by FDA Commissioner Margaret A. Hamburg, M.D., explained that the purpose of the blog is for senior FDA leadership and staff to explain topics about the work done at FDA that they think would be of interest to the American public. While FDA Voice is very new, it has already featured three blogs from Hamburg and several from other key FDA leadership, such as the Director of the Center for Devices and Radiological Health, Jeffrey Shuren, M.D., J.D. Some of the first topics have featured FDA explaining FDA's views and responses to criticisms concerning FDA's medical device program, FDA's advisory committee process and recent questions raised about the potential for a conflict of interest, particularly financial interests, as well as FDA's recent user fee proposals sent to Congress, which we reported on yesterday. Other topics appear to be more akin to what you might find elsewhere on FDA's website concerning consumer information, such as how to read a children's medication label.

In addition to the blogs themselves, FDA Voice offers links to news items on FDA's website and FDA's presence in the social media, including Facebook and Twitter. FDA Voice joins other FDA "transparency initiatives" such as its own FDA Transparency Blog.

FDA Lawyers Blog wishes FDA Voice success in its launch and looks forward to its new insight into FDA's thinking and procedures.

by Brian Malkin

On January 13, FDA announced that the Secretary of Health of Human Services Kathleen Sebelius sent Congress FDA's three user fee program proposals. The programs included the fifth reauthorization of the Prescription Drug User Fee Act ("PDUFA V") and two new programs, one for a new biosimilars program called Biosimilar and Interchangeable Products User Fees and one for generic drugs called Generic Drug User Fees ("GDUF"). All user fee programs are essentially agreements for industry to pay fees to help fund a portion of FDA's initial and ongoing product reviews, where FDA agrees to overall performance goals, including a certain percentage of all new applications to be reviewed within certain time periods. We have reported on these user fee proposals throughout the year with some highlighted below.

Speaking to the new proposal, FDA Commissioner Margaret A. Hamburg, M.D. said, "These final recommendations offer a great example of what can be achieved when the FDA, industry and other stakeholders work together on the same goal. At a time of greater budgetary constraint, user fees provide a critical way for leveraging appropriated dollars, ensuring that FDA has the resources needed to conduct reviews in a timely fashion. . . . Human drug user fees have revolutionized the drug review process in the United States since they were adopted 20 years ago, allowing the FDA to speed the application review process without compromising the agency's high standards."

Congress passed PDUFA I in 1992, creating a user fee program that requires reauthorization every five years. Each user fee program establishes specific yearly fees and performance goals set by industry representatives and patient and consumer advocates in consultation with FDA. PDUFA V negotiations have been going on even since 2010, which we reported on, for example, here. FDA's most recent meeting discussing PDUFA V was held on October 24, 2011, with a transcript here.

by Kyle Deighan

The job "pharmacist" likely hasn't traditionally been considered a dangerous profession with the likes of firefighters, police officers, and fishermen. That perception may soon change, however, as pharmacies have increasingly become a popular target for armed robberies. According to the United States Drug Enforcement Administration ("DEA"), the number of pharmacy robberies rose from about 380 in 2006 to about 700 in 2010, an increase of about 80 percent. In state of New York, for example, pharmacy robberies jumped from only 4 in 2006 to 30 in 2010. Sadly, several of these have resulted in deaths.

When it comes to robbing pharmacies, the thieves are after more than just the money in the cash register--they are looking for prescription drugs. Drugs such as pain relievers OxyContin® (oxycodone hydochloride) are favorite targets, leading many pharmacies to increase security and post signs that they do not carry specific drugs.

DEA spokesperson Rusty Payne explained: "What's usually the reason for drug crime? Addiction and money . . . There's a lot of money in illicit trafficking of pharmaceuticals and we've seen abuse go through the roof. People do crazy things when they're on drugs." Indeed, the number of Americans on prescription drugs for reasons other than medical necessity is staggering. According to FDA's estimates, 33 million Americans misused opioids, drugs used to treat pain, in 2007 alone. The National Institute of Drug Abuse ("NIDA") estimates that 73% of all prescription drug abuse is with pain relievers.

by Scot B. Pittman

FDA's Center for Veterinary Medicine ("CVM") announced last week that it was restricting the use of certain antibiotics in farm animals. On January 6, 2012, CVM published a final rule in the Federal Register that prohibits certain uses of cephalosporin drugs in food-producing animals. The rule is a modification of FDA's 2008 order banning all extralabel uses of cephalosporins in food producing animals. The roughly 170 comments in response to the 2008 proposal convinced FDA that the ban was too broad.

Specifically, the new rule prohibits certain extralabel uses of cephalosporin drugs in cattle, swine, chicken, and turkey. Included among the prohibitions are:

• Using cephalosporin drugs at unapproved dosage levels, frequencies, durations, or routes of administration;
• Using cephalosporin drugs in cattle, swine, chickens, or turkeys that are not approved for use in those species; and
• Using cephalosporin drugs for disease prevention.

• Extralabel use of approved cephapirin products in food-producing animals;
• Use to treat or control an extralabel disease indication, provided that the use adheres to a labeled dosage regimen approved for that particular species and production class; and
• Extralabel use in food-producing minor species (e.g. ducks and rabbits).

by Howard E. Rosenberg, Ph.D.

The recent editorial in the British Medical Journal ("BMJ ") by Richard Lehman and Elizabeth Loder, highlights the authors' grave concerns about missing clinical trial data, data which by now should have been published. This lack of information is perceived in the editorial as being a distinct threat to the integrity of evidence-based medicine.

As the authors point out, clinical research aims to reduce clinical uncertainty by performing experiments on groups of people who consent to run the risks of such trials in the belief that the resulting knowledge will benefit others. Their concern was voiced particularly after the publication of a study in the BMJ by Andrew Prayle, Matthew Hurley and Alan Smyth, which examined the compliance with mandatory reporting of summary clinical trial results (within one year of completion of trial) on ClinicalTrials.gov for studies that fall under the Food and Drug Administration Amendments Act ("FDAAA") legislation.

The study by Prayle et al. takes as its premise that the key principle in the good conduct of clinical trials is that a summary of the trial protocol should be freely available while the study is ongoing and that, on completion of the study, the results should be readily accessible to all in a timely fashion. As they point out in their paper; in February 2000 the Food and Drug Administration Modernization Act ("FDAMA") prompted the creation of a national clinical trials registry in ClinicalTrials.gov. FDAAA required the registration of summaries of trial protocols for "applicable clinical trials" (i.e., clinical trials that are covered by the FDAAA). These are clinical trials that (1) have at least one site in the United States, (2) are of a drug, device, or biological agent; and (3) are "initiated or ongoing as of September 2007," excluding phase I studies and early feasibility trials of devices.

by Brian Malkin

Late last year, FDA announced a new standard operating procedure ("SOP") for managing review staff changes during the review of premarket approval applications ("PMAs") for medical devices. According to the SOP, the goal of the SOP is to help provide more consistent feedback and guidance to medical device applicants, particularly when there is staff turnover. The SOP replaces an older guidance from 1990.

The SOP states that "As a general matter, a newly assigned review team member is expected to follow the decisions and advice given by the individual he or she is replacing." If the new review team member identifies a need to change in the amount or type of information, however, the SOP now mandates a policy that this new member obtains appropriate supervisory concurrence before so informing applicants:

To promote consistency and to assure that any significant proposed changes are sufficiently justified, the newly assigned review team member must seek appropriate supervisory concurrence prior to contacting the submitter about the identified issue. In other words, when staff becomes aware of information that may alter the information and data required for premarket review, they should receive concurrence from the appropriate management level before taking any action.

For proposed changes in data requirements, staff should ask for data that imposes the least justified burden on the applicant.

by Scot B. Pittman

On January 3, FDA released proposed amendments to its regulations governing submitting citizen petitions and petitions for stay of action ("PSAs") that involve requests for FDA to take action regarding pending abbreviated new drug applications ("ANDA") or 505(b)(2) new drug applications ("NDAs"). The changes are meant to execute provisions in the Food and Drug Administration Amendments Act of 2007 ("FDAAA") (Pub. L. 110-85).

Citizen Petition Regulation Amendments

Specifically, the proposed changes are meant to address Section 505(q) of FDAAA (21 U.S.C. § 355(q)) and codify certain aspects of FDA's thinking presented in its Guidance on 505(q) citizen petitions, which we reported on here. Enacted in September 2007, section 505(q) governs how FDA handles certain citizen petitions and PSAs that call for any form of action related to pending ANDA or 505(b)(2) NDAs. FDA notes that it receives many petitions asking it to delay approving an ANDA or 505(b)(2) NDA until certain criteria in the petition have been met. While many of these petitions, especially if submitted early in the approval process, can aid FDA, some, especially those submitted late in the review process raising minimally valid scientific or legal issues, can improperly delay the approval of an application.

by Brian Malkin

On December 29, FDA announced that immediate -release transmucosal fentanyl products would have a shared Risk Evaluation and Mitigation Strategy ("REMS") that would replace the individual REMS presently in place for approved products in this category. In addition to other benefits, the single shared system would permit prescribers and pharmacies to enroll in one system rather than multiple, similar REMS programs. The shared REMS is called the Transmucosal Immediate-Release Fentanyl ("TIRF") REMS Access Program and will become effective in March 2012.

Presently, the list of affected brand-name drugs includes Abstral®, Actiq®. Fentora®, Lazanda®, and Onsolis®. which are all opioid drugs indicated to manage pain in cancer patients, who routinely take other opioid pain medications on a continual basis. Breakthrough pain is pain that comes on suddenly for short periods of time and cannot be reduced by a patient's normal pain management program. For TIRFs to be used safely, they must be used by patients who are already opioid tolerant based on their concurrent regular use of another opioid pain medication.

Janet Woodcock, M.D., Director of the Center for Drug Evaluation and Research ("CDER") said, "This TIRF REMS will ensure safe use and access to these drugs for patients who need them. We have worked with the sponsors of both the innovator and generic drugs to develop this single, shared system that will streamline the process and decrease the burden of the REMS on the health care system."

by Kyle Deighan

Last week, FDA warned health care professionals to exercise caution when dispensing the FDA-approved eye medicine DUREZOL® (difluprednate ophthalmic emulsion) 0.05% and the unapproved prescription topical wart remover DURASAL® (salicylic acid) 26%. This comes after several reports of injuries caused when patients expecting to receive DUREZOL®, the eye medicine approved for the treatment of inflammation and pain associated with ocular surgery, were inadvertently given DURASAL®, an unapproved wart remover. One such incident resulted in a $1 million lawsuit against Walgreens, filed by a man who put the acid wart remover in his eye after ocular surgery. Although the packaging contained the explicit instructions "not for use in eyes," the man was using the eye drops to recover from eye surgery and was likely unable to read the warning. Perhaps the most troubling aspect of this story is that reports regarding possible confusion between DUREZOL® and DURASAL® go as far back as 2009.

In its report last week, FDA cautioned that pharmacists should exercise care when filling prescriptions for the eye medicine due to the potential for confusion between the names of the two medications. Obviously, this highlights a concerning issue that can arise with drugs that do not undergo the standard FDA approval process. Generally, as part of the drug approval process, FDA screens the proprietary names of proposed drugs for similarities with other products on the market. However, DURASAL® (the wart remover), did not undergo FDA's approval process, and was not screened to evaluate potential name confusion with other approved products prior to entering the market. As we have written about previously (such as here), thousands of unapproved drugs remain on the market (including over-the-counter ("OTC") drugs that also do not undergo a pre-approval process but are legal if they follow FDA's monographs) and problems such as this continue to crop up. FDA encourages health care professionals and patients to carefully examine packaging and labeling to avoid confusion.

As for DURASAL®, according to FDA, Elorac Inc., the distributor of DURASAL®, has not responded to requests from FDA to remove the product from the market or recalled the product from shelves. DURASAL® contains an active ingredient approved for wart removal but in an amount that exceeds the maximum concentration permitted for an OTC drug, which is why it is an unapproved drug. Interestingly, Elorac Inc.'s website does not list DURASAL® as one of its products, yet information about DURASAL® is still available through Elorac when the page www.durasal.com is accessed. Elorac continues to manufacture another product containing salicyclic acid in a slightly higher amount and in a different vehicle called VIRASAL®, which also does not appear to have FDA approval, based on FDA's list of approved drugs. Both DURASAL® and VIRASAL® state on their prescribing labeling "Rx only / FOR TOPICAL USE ONLY. / NOT FOR OPHTHALMIC, ORAL OR INTRAVAGINAL USE", which explains in part why some pharmacists may have been confused given that both DUREZOL® and DURASAL are labeled as prescription products.