ADHDBrainWaveDevice.jpgOn July 15, FDA announced its approval of the first brain- function-based medical device to help diagnose attention deficit hyperactivity disorder (“ADHD”) in children and adolescents. The approved device, the Neuropsychiatric Electroencephalogram-Based Assessment Aid (“NEBA”) System, uses an electroencephalogram (“EEG”) to measure brain waves with sensors attached to a child’s head, which are wired to a computer. After fifteen to twenty minutes of information-gathering, it provides a read-out of the types and timing of electrical impulses, i.e., waves, emitted by brain nerve cells. Because two kinds of brain waives–theta and beta–may be more common in ADHD children, physicians can use this information to confirm an ADHD diagnosis or direct further diagnostic testing.

EEG technology has been around since the early 1900s and is often used to diagnose sleep disorders, measure unconsciousness, evaluate the brain post-head trauma, and monitor the brain during surgery. ADHD, which results in attention difficulties, hyperactivity, impulsivity and behavioral problems, is one of the most common neurobehavioral disorders in childhood. According to the American Psychiatric Association, nine percent of U.S. adolescents have ADHD and the average age of diagnosis is seven years. “Diagnosing ADHD is a multistep process based on a complete medical and psychiatric exam,” explained Christy Foreman, director of the Office of Device Evaluation at the FDA’s Center for Devices and Radiological Health (“CDRH”)

The manufacturer of the NEBA System, NEBA Health of Augusta, Georgia, provided FDA with data including a clinical study that evaluated 275 children and adolescents (ages 6 to 17 years) with attention/behavioral issues, using both the approved device and standard diagnostic testing such as questionnaires and physical exams. An independent group of ADHD experts also reviewed the data and reached a consensus as to whether each subject had ADHD. According to FDA, the side-by-side results “showed that the use of the NEBA System aided clinicians in making a more accurate diagnosis of ADHD when used in conjunction with a clinical assessment for ADHD, compared with doing the clinical assessment alone.”
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On July 25 and 26 FDA will hold a Public Meeting at its White Oak campus on risk evaluation and mitigation strategies (“REMS”). FLH Partner Brian J. Malkin plans to attend to take advantage of many of the lessons learned at a recent Q1 Productions Global Risk Management Conference blogged on here. Mr. Malkin is schedules to speak on a panel on Thursday, July 25, on shared REMS. According to FDA’s website for the Public Meeting topics to cover include:

[I]nput on issues and challenges associated with the standardization and assessment of risk evaluation and mitigation strategies (REMS) for drug and biological products. As part of the reauthorization of the Prescription Drug User Fee Act (PDUFA), FDA has committed to standardizing REMS to better integrate them into, and reduce their burden to, the existing and evolving health care system. As part of the PDUFA commitments, FDA will also seek to develop evidence-based methodologies for assessing the effectiveness of REMS.

To obtain input from stakeholders about REMS standardization and evaluation, FDA will hold a public meeting to give stakeholders, including health care providers, prescribers, patients, pharmacists, distributors, drug manufacturers, vendors, researchers, standards development organizations, and the public an opportunity to provide input on ways to standardize and assess REMS.

ITC Building.pngSection 337 investigations before the International Trade Commission (“ITC” or “Commission”) already proceed at a fast pace. But in keeping with its goal of completing investigations expeditiously, on June 24, 2013, the Commission announced its plan to speed up the process. The Commission stated in a press release that it will select certain investigations for inclusion in a new dispositive-issue pilot program. For an investigation that contains potentially case-dispositive issues–including the existence of a domestic industry, whether proof of importation of an accused product exists, and whether the complainant has standing to participate in an investigation–the Commission will direct the assigned Administrative Law Judge (“ALJ”) to resolve the dispositive issues within 100 days of institution of the investigation.

Under current ITC practice, an ALJ does not rule on such dispositive issues until the summary-determination stage of an investigation or until he or she issues an initial determination after a trial-type hearing. Both of these events, however, occur after months of discovery have taken place on all issues, dispositive and non-dispositive alike. And in the summary-determination stage, the ALJ may find that issues of fact prevent resolution of the investigation without holding a hearing on all pending issues. By this time, the parties have expended considerable resources litigating the investigation. The pilot program seeks to “limit unnecessary litigation, saving time and costs for all parties involved.”

For an investigation assigned to the program, the Commission will direct the ALJ to rule on a specific dispositive issue early in the investigative process. For instance, under 19 U.S.C. § 1337(a)(2)-(3), complainants accusing respondents of importing products that infringe the complainants’ intellectual-property rights must establish that a domestic “industry” exists or is in the process of being established in the United States with respect to those rights. If the Commission determines at the institution of the investigation that a particular complainant likely cannot establish the existence of a domestic industry, it will direct the ALJ assigned to that case to “rule on that issue early in the investigation through expedited factfinding and an abbreviated hearing limited to the identified issue.”
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troll.jpgLarge companies have long pointed to non-patent entities (“NPEs”) for abusing the patent system by buying patent portfolios and using litigation, or the threat thereof, to force licensing fees and settlements. In contrast, the patent-holding companies argue that they are asserting legally-obtained rights against huge corporations that are using other people’s innovations for profit. Based on legislation in Congress, as well as a proposal from President Barack Obama, it appears that the desire for anti-“patent troll” measures is gaining traction by both parties. The legislation has primarily taken a practical approach of targeting problematic tactics used by NPEs. Six pieces of legislation have been introduced or proposed in Congress including the Shield Act, the Patent Abuse Reduction Act, the End Anonymous Patent Act, the Patent Quality Improvement Act, and an act introduced by the leaders of the House and Senate Judiciary Committees.

The Saving High-Tech Innovators from Egregious Legal Disputes Act of 2013, or Shield Act, (H.R. 6245) was introduced in the House in February. It defines a “troll” as a patent owner who did not do the inventing behind the patent and does not exploit it by making a product. A patent owner that fits those criteria and loses an infringement case would be responsible for its opponents’ costs under the Bill. The Bill would also allow an accused infringer to move early in the case for a judgment that the patent owner is a NPE required to pay litigation costs if it loses.

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Written by Shelly Fujikawa. Ph.D

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The Patent Abuse Reduction Act (S. 1013), introduced in the Senate in May, would mandate that any patent infringement complaint include 14 separate pieces of information that are not currently required. The requirements include identifying each product or feature alleged to infringe the patent, including name or model number; an explanation of how the asserted claim corresponds with the accused function “with detailed specificity,” a description of the plaintiff’s principal business and right to assert the patent; and a list of every other suit in which the patent has been asserted. To reduce discovery costs, the Bill would require any party in patent litigation to cover the cost of discovery beyond “core documentary evidence,” which includes documents that relate to the conception of the patent and potentially invalidating prior art. The Bill would also mandate that the prevailing party in patent litigation be awarded reasonable costs and expenses, including attorneys’ fees, unless “the position and conduct of the nonprevailing party were objectively reasonable” or “exceptional circumstances make such an award unjust.”
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lung-cancer-500x360.jpgFriday, FDA approved Boehringer Ingelheim’s drug, Gilotrif® (afatinib), to treat patients with late-stage metastatic Non-Small Cell Lung Cancer (“NSCLC”). Gilotrif® is a tyrosine kinase inhibitor that inhibits cancer-causing proteins. NSCLC is any type of epithelial lung cancer other than small cell lung cancer (“SCLC”). The most common types of NSCLC are squamous cell carcinoma, large cell carcinoma, and adenocarcinoma. Although NSCLCs are associated with cigarette smoke, adenocarcinomas may be found in patients who have never smoked. As a class, NSCLCs are relatively insensitive to chemotherapy and radiation therapy compared with SCLC.

Gilotrif® targets specific proteins caused by epidermal growth factor receptor (“EGFR”) gene mutations, which are present in about 10 percent of NSCLC patients. Specifically, Gilotrif® targets proteins expressed by EGFR exon 19 deletions and exon 21 L858R substitutions. The drug is being approved concurrently with a companion diagnostic kit that helps determine if a patient’s lung cancer cells express EGFR mutations. The kit is called therascreen EGFR RGQ PCR Kit, and is made by Qiagen N.V.

FDA approval of Gilotrif® for NSCLC is a big deal. Lung cancer is the number one cause of cancer-related deaths and NSCLC makes up about 85% of all lung cancers. An estimated 160,000 people will die in the U.S. from lung cancer this year, according to the National Cancer Institute, and 1.38 million deaths worldwide are attributable to lung cancer. Lung cancer is the cause of 18% of all cancer deaths.
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magnifying glass.jpgOn July 12, 2013 FDA issued new Guidance for Industry: Circumstances that Constitute Delaying, Denying, Limiting, or Refusing a Drug Inspection. The Guidance document illustrates circumstances where the FDA will treat the occurrence as contrary to section 501(j). These are divided into four sections: (1) Delay of Inspection, (2) Denial of Inspection, (3) Limiting of Inspection, and (4) Refusal to Permit Entry.

Background

FDA, under the jurisdiction of the Federal Food, Drug & Cosmetic Act (“FD&C Act”) Section 704(a), has the authority to carry out inspections of facilities by duly appointed FDA employees. These inspections are to be undertaken at reasonable times, within reasonable limits and in a reasonable manner.

FDA has not always been able to carry out its tasks. Consequently, in light of the recent Food and Drug Administration Safety and Innovation Act (“FDASIA”), which was signed into law in July 2012, and in particular Section 707 of FDASIA, which added 501(j) to the FD&C Act, the FDA now deems as adulterated a drug that “has been manufactured, processed, packed, or held in any factory, warehouse, or establishment and the owner, operator, or agent of such factory, warehouse, or establishment delays, denies, or limits an inspection, or refuses to permit entry or inspection“. (emphasis added)
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RISK.jpgOn July 11-12, Q1 Productions hosted a conference, Global Risk Management & Regulatory Policy. In some ways, the conference served as an industry-focused prelude for discussion of many of the topics that plan to be discussed at an upcoming FDA meeting on July 25 and 26 on Standardizing and Evaluating Risk Evaluation and Mitigation Strategies (“REMS”). The Conference featured presenters from industry, academia, consultants, and law, where controversial topics such as REMS assessments and shared REMS could be discussed by both innovator and generic companies in a collaborative setting.

The Conference started off with two presentations designed to provide a set of tool kits for optimizing REMS for maximum risk management effectiveness (Barbara Troupin, MD, MBA, Vice President, Scientific Communications & Risk Management, Vivus), and streamlining them for efficiency (Charles Tressler, Senior Director of Safety Surveillance & Risk Management). Christopher Milne, DVM, MPH, JD, Director of Research, Tufts Center for the Study of Drug Development, next presented an overview of a REMS report issued by the Office of Inspector General (“OIG”), Department of Health and Human Resources, entitled, “FDA Lacks Comprehensive Data to Determine Whether Risk Evaluation and Mitigation Strategies Improve Drug Safety” issued in February 2013. Milne explained that the OIG found that FDA’s experiment of essentially renaming risk management programs from Risk Minimization Action Plans (“RiskMAPs”) to REMS did not appear to be much of an improvement (only 22% thought it was better). The OIG found that sponsors were developing REMS too late in the product development, inconsistently submitting the required assessment reports, and the assessment reports were either incomplete or not useful to determine whether the product’s risks were being appreciably reduced by the REMS.

Milne believes that FDA is holding the upcoming public REMS meeting and has proposed a five-year analysis and integration plan to prevent further Congressional attention to REMS in the next prescription drug user fee act (“PDUFA”), expected in 2017. According to Milne, every year FDA plans to carefully review one REMS with Elements to Assure Safe Use (“ETASU”), e.g., restricted pharmacy settings or specialized training for physicians and pharmacies, registries, to improve its efficiency and risk minimization tools. Milne suggested (and various conference attendees agreed) a REMS 101-type of class is likely needed to make REMS more productive. For instance, it would be useful to collect public information about the pros and cons of all REMS tools, as well as consider ways to make REMS implementation less burdensome for physicians and patients alike. Milne noted that there are now case studies demonstrating that REMS place a large burden on patients and the health system, denying patients access to certain needed drugs with a REMS. And at the same time, sponsors are unsure what elements to include in their REMS, because FDA can at the same time complain that a REMS fails to disclose offlabel use risks, while at the same time allege that the REMS misbrands the product by suggesting the offlabel uses.
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On July 11, FLH Partner Brian J. Malkin will speak at Q1 Productions’ Global Clinical Risk Management & Regulatory Policy Conference in Alexandria, VA on the topic “Developing a Single, Shared REMS in a Collaborative Setting”. The session description reads:

The FDA approves single, shared REMS for product categories with similar risk management programs to help relieve some of the burden on healthcare providers and pharmacies. The development of shared REMS requires that multiple companies and the FDA work in tandem to unify data and risk minimization systems, a model which some companies have also used to help organize risk management plans internationally. By ensuring a strong cross-corporate collaboration, internal regulatory policies, data analysis and communication systems can be synchronized internationally for advanced risk management programs.

  • Structuring lines of communication within shared REMS network

pharmacy.pngCompounding pharmacies have been on FDA’s priority list since the 61 deaths and 749 cases of fungal infections from steroid injections contaminated during manufacture by New England Compounding Center (“NECC”), last fall. When appearing before Congress last November, FDA Commissioner Margaret A. Hamburg, M.D. plead a lack of regulatory authority in the wake of the Western States U.S. Supreme Court decision. Arguably, it is unclear if Western States struck down just the regulation of advertisements (as industry has contended) leaving the regulatory structure untouched or if it invalidated the authorization of compounding pharmacies (as FDA has contended, since the 9th circuit held the provisions not-severable and that decision was affirmed), leaving compounding pharmacies technically illegal but ignored by FDA regulatory discretion. Either way, FDA appeared to retain certain regulatory authority over compounding pharmacies, but FDA’s scope was unclear.

Congress did not want to leave the deaths resulting from compounded drugs alone, so S. 959 was proposed to fix the problem, despite the lack of clarity what problem needed to be fixed. Among other things, S. 959 would forbid compounding pharmacies to copy FDA-approved but nonpatented medicines. But do we want all medications (including compounded drugs) to require premarketing approval? Do we want more frequent inspections of compounding pharmacies, and if so how do we pay for it? Do we just want someone to be held responsible–who: FDA, pharmacy boards, or someone else?

The basic dilemma is simple: we want safe and effective medicines, but we also want them at a price that we can afford. Compounding pharmacies may provide certain formulations of medicines without the overhead and costs related to commercially-manufactured and regulated medications. In some instances, compounding pharmacies may be able to offer medications with the same active compounds used in conventional drugs but with different inactive ingredients at lower costs than commercial medications. When such pharmacies are too small, few people realize the benefits of customized medications due to availability or cost. When they are too big, they are viewed as traditional drug manufacturers by FDA, leading to questions about what regulatory oversight is appropriate or warranted.
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globalmap.pngThe Global Clinical Risk Management and Regulatory Policy Conference will take place in Alexandria, Virginia on July 11-12, 2013. Throughout the two-day program, executives from industry will have an opportunity to discuss and debate the many challenges associated with profiling the risk of products as well as minimizing these risks and meeting regulatory expectations. With a well-rounded speaking platform that includes not only industry representation but also regulatory bodies, legal perspectives and the healthcare professional, participants will have an unrivaled opportunity to engage, network and learn from leading executives and corporations.

As with all Q1 programs, the focus of the event will not only lie upon the educational content, but also providing attendees with an opportunity to network and build relationships across this highly dynamic and evolving market. For conference sponsors supporting this program, the event will be an ideal vehicle for both learning more about advanced RMPs, but also an opportunity to disseminate information regarding products and services supporting pharmaceutical risk management.

KEY CONFERENCE TAKEAWAYS

  • Harmonizing risk management strategies for global markets
  • Measuring the effectiveness of approved REMS & RMP
  • Working with regulatory agencies to revise risk plans
  • Forecasting the FDA’s next steps in determining REMS drug safety improvement
  • Strengthening benefit-risk analysis on an international scale
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