On September 11-12, FLH’s Partner Brian J. Malkin will attend GPhA[Generic Pharmaceutical Association]/FDA’s ANDA [Abbreviated New Drug Application] Labeling Workshop / USP [United Pharmacopeial Convention] User Forum. The Conference provides a unique opportunity for attendees to hear straight from FDA’s Office of Generic Drugs (“OGD”) Labeling Review Staff, who are responsible for reviewing and approving ANDAs. The Workshop will provide industry with current information on the ANDA labeling review process as well as the many issues facing the generic industry when submitting ANDA labels. Some key topics to cover include:

  • Recommendations for industry on handling last-minute labeling “carve-outs”
  • The impact of REMS on the ANDA labeling review process
  • MedGuide Requirements>

functional foods.jpgOn September 10, 2013, the Food and Drug Law Institute (“FDLI”) hosted a conference, “Safeguarding the Functional Food and Dietary Ingredient Supply Chain“. The Conference concerned a variety of emerging requirements and compliance issues for functional foods and dietary ingredient or supplement manufacturers and distributors in view of the FDA Food Safety Modernization Act (“FSMA”). Signed into law on January 4, 2011, FSMA has been called “the most sweeping reform of our food safety laws in more than 70 years.” Among other things, FSMA shifts the focus from responding to contamination to preventing it to ensure the U.S. food supply is safe.

The Conference Keynote, Daniel Fabricant, Ph.D., FDA’s Director, Division of Dietary Supplement Programs, Center for Food Safety and Applied Nutrition, Office of Foods and Veterinary Medicine, remained throughout the program and provided insights regarding FDA’s view on “functional foods” and dietary ingredients. First off, FDA has not officially recognized that there are “functional foods”, despite understanding that many people are self-treating based on information gleaned on the Internet or elsewhere with the hopes to either prevent or mitigate potential or current health issues. According to Fabricant, while dietary supplements may make certain health (structure/function) claims with adequate scientific evidence, FDA does not authorize foods to make health claims; instead, FDA considers foods to make statements about taste, aroma, and nutritive values.

In Fabricant’s view, it is not clear where industry should go when looking for guidance on functional foods, which are viewed by industry as foods with legal structure/function claims. FDA is concerned about the potential for harm: (1) invisible (hard to detect), (2) conscious (deliberately tainted), or (3) catastrophic (affects many people). Fabricant suggested that energy drinks, for example, have been suggested as a functional food, but many of these products include caffeine, which is a drug or conventional food. But the physical attributes of the product is not the primary determinant. Here, FDA is developing guidance to distinguish liquid dietary supplements from conventional, food-type beverages. What FDA has seen is that companies engage in “category hopping” to pick the category that where they best meet the requirements, but good manufacturing practices (“GMPs”) often remain an issue. And in FDA’s view, many products over rely on “bad” information rather than “competent and reliable scientific evidence.” Here, FDA looks whether a particular claim is substantiated– what is the meaning of claim, the relationship of scientific evidence to the claim, the quality of evidence, and the totality of evidence in view of the claim. The biggest “pitfall” Fabricant mentioned is an over-reliance on disease treatment studies and confusion regarding intended use.
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On September 10, 2013, FLH’s Partner Brian J. Malkin will be attending the Food and Drug Law Institute’s (“FDLI”) Conference, “Safeguarding the Functional Food and Dietary Ingredient Supply Chain“. The Conference will address a variety of compliance issues and the emerging requirements for functional foods and dietary supplement manufacturers and distributors in view of the FDA Food Safety Modernization Act (“FSMA”). FSMA has been called “the most sweeping reform of our food safety laws in more than 70 years” and was signed into law by President Obama on January 4, 2011. FSMA shifts the focus from responding to contamination to preventing it to ensure the U.S. food supply is safe.

Conference attendees will hear from top FDA officials. For example, the Conference features a Keynote Address from the Director of FDA’s Division of Dietary Supplement Programs, Daniel Fabricant, Ph.D. In addition, industry experts will provide insight on how FDA may implement FSMA’s supplier verification requirements of the Food Safety Modernization Act (FSMA). In particular manufactures will gain a greater understanding of what regulatory requirements can be expected in the coming months by discussing the key regulatory provisions of supply chain safety, the differing definitions for ingredients used in functional foods versus ingredients used in dietary supplements, and by analyzing trends in supply chain quality testing.

Thumbnail image for Thumbnail image for Thumbnail image for Q1 ProductionisPreserving the Integrity and Quality of Captured Data through the Utilization of Innovative Technologies and EDC Systems while Effectively Managing Limited Resources and Oversight of Outsourced Clinical Data Management Team

Throughout the life science industry, executives responsible for clinical data management face a host of escalating challenges as regulatory authorities and internal stakeholders continually demand increased levels of data from clinical studies. As trials have evolved and taken on a role where they are exploring a wide variety of concerns, from regulatory clearance to reimbursement and economic support, the amount of data, and therefore the role of the clinical data manager have become increasingly complex. Adding to this challenge are clinical sites overburdened with multiple studies being conducted simultaneously, varied systems for data collection and entry as well as pressure from clinicians who want the data accessible as soon as possible. Within all of these challenges caused by varied stakeholders, clinical data managers are harnessing technology and new solutions in ways not seen previously, to enable their corporations to excel in research and development and to meet their scientific goals.

This two day conference will take place in Alexandra, Virginia on October 28-29, 2013. Innovative strategies and technologies used by forward thinking companies will be the cornerstone of this conference program, as presenters and audience members discuss methods for ensuring the integrity and quality of clinical data, the evaluation and selection of new technological systems, as well as strategies for ensuring data meets increasingly rigorous FDA requirements. Case studies will show hands on application of advanced technologies, allowing participants an opportunity to road-test the latest and greatest technologies available on the market.
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Thumbnail image for 120px-Components_of_a_MiniCiggy_e-cigarette.jpgOn September 5, the Centers for Disease Control and Prevention (“CDC”) released a Morbidity and Mortality Weekly Report “Electronic Use Among Middle and High School Students – United States, 2011-2012“. According to the Report, electronic cigarette or “e-cigarette” use among middle and high school students doubled in just one year from 4.7 percent in 2011 to 10.0 percent in 2013. In the same period, high school students using e-cigarettes within the last 30 days rose from 1.5 to 2.8 percent. Yet among current e-cigarette users in high school (2012), 80.5% reported current conventional cigarette smoking, and current use of both e-cigarette and conventional cigarettes increased from 1.2% to 2.2%.

E-cigarettes are designed to look and feel like conventional cigarettes but do not ignite tobacco leaf products. Instead, they include a vaporizer or atomizer, powered by a battery and controlled by a sensor and microcomputer chip, which heats and vaporizes fluid in a cartridge containing various chemicals. These chemicals often include liquid nicotine derived from natural tobacco plants. Back in 2011, we blogged on an FDA announcement that the Agency would regulate e-cigarettes as “tobacco products” under Family Smoking Prevention and Tobacco Control Act of 2009. At that time, FDA was reacting to a loss that the Agency had in Sottera, Inc. v. FDA, where FDA first had attempted to regulate e-cigarettes as combination drug/devices. In Sottera, the D.C. Circuit Court of Appeals concluded that unless the e-cigarettes were marketed with therapeutic claims, such as smoking cessation or reduction, FDA had the authority to regulate e-cigarettes as “tobacco products,” because the nicotine used in the products was obtained from tobacco leaves.

To date, however, FDA has not issued regulations to expand its jurisdiction for “tobacco products” to include e-cigarettes, and, as a result, FDA has little information to understand the types of components or potentially-harmful ingredients contained therein. According to the CDC’s Press Release covering this topic, FDA’s Director for the Center for Tobacco Products, Mitch Zeller, said reacting to the CDC’s Report, “These data show a dramatic rise in usage of e-cigarettes by youth, and this is cause for great concern as we don’t yet understand the long-term effects of these novel tobacco products. . . . These findings reinforce why the FDA intends to expand its authority over all tobacco products and establish a comprehensive and regulatory framework to reduce disease and death from tobacco use.” So while it remains unclear when FDA will act to regulate e-cigarettes, FDA still seems committed to do so.
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RISK.jpgFLH Partner Brian J. Malkin was recently featured in an InsideHealthPolicy’s article, “Buprenorphine Decision Spurs Further Call For Shared REMS Rulemaking” The article focused on various suggestions for FDA to initiate rulemaking for shared REMS programs in view of a failed attempt to share a risk evaluation and mitigation strategies program (“REMS”) for buprenorphine-containing transmucosal products for opioid dependence (“BTOD”). In the end, FDA permitted a group of generic manufacturers to form their separate but similar shared BTOD REMS.

FDA has not explained the expectations for a shared REMS other than it is up to the parties to negotiate one or request a waiver from FDA if certain conditions are met. The Food and Drug Administration Amendments Act of 2007 (“FDAAA”) required generic manufacturers to share certain REMS with Elements to Assure Safe Use (“ETASU”). ETASU REMS include some form of restricted distribution, such as only in hospital settings or certain “registered” pharmacies or prescribed only by physicians with special training or following evidence of safe-use conditions. FDA may waive the shared REMS requirement, if FDA determines the burden of creating a single, shared REMS between competitors outweighs the benefits or an aspect of the ETASU is claimed by a patent, the patent has not expired, and the generic applicant(s) has/have sought a license but was unable to secure a license. If waived, the generic applicant(s) must use a comparable element to assure safe use of the product.

Some of the quotes from Mr. Malkin the article include:

Brian Malkin, a partner at Frommer Lawrence & Haug, said FDA should initiate rulemaking and issue guidance on the shared REMS negotiation process, and consider providing branded companies an incentive like exclusivity to encourage participation in shared risk mitigation plans. The comments came during a public meeting where FDA sought input on standardizing REMS. Drug industry groups and other stakeholders encouraged FDA to limit standardization efforts to drugs with similar risk profiles

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research.jpgOn August 27, 2013, FDA issued a new guidance, “IRB Responsibilities for Reviewing the Qualifications of Investigators, Adequacy of Research Sites, and the Determination of Whether an IND/IDE is Needed“. An IRB is an appropriately-constituted group that has been formally designated to review and monitor biomedical research involving human subjects. Following FDA’s regulations, an IRB has the authority to approve, require modifications in (to secure approval), or disapprove research. Accordingly, IRBs serve an important role in the protection of the rights and welfare of human research subjects.

The Guidance applies to drugs, biologics, and medical devices and was developed in consultation with the Department of Health and Human Services Office for Human Research Protections (“OHRP”), largely based on recommendations from previously-issued resources. FDA said that it issued the guidance to clarify the Institutional Review Board (“IRB’s”) responsibilities related to the selection of clinical investigators and research sites, because these items are normally considered a sponsor’s responsibility yet they have an impact on the rights and welfare of study subjects. The recommendations in the guidance apply to any IRB, whether serving as a local or centralized review process for multi-site studies. This guidance was developed as part of FDA’s and OHRP’s efforts to harmonize the agencies’ requirements and guidance for human subject protection.

While sponsors of clinical research select clinical investigators who are “qualified by training and experience as appropriate experts,” IRBs have a role in reviewing the investigators’ qualifications to conduct clinical research as proposed in a study protocol. Depending on the IRB’s relationship to the institution conducting the investigation and knowledge of the research, the IRB may already know that a proposed investigator is qualified to conduct the research or may need to dig deeper. In particular, for more high risk investigations, FDA and OHRP expects IRBs to apply a greater amount of scrutiny, especially if the study involves a sponsor-investigator, is outside the investigator’s expertise, or involves other characteristics that may increase risk to human subjects. For example, an IRB may observer, or have a third party observe, the consent process and the research.
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Thumbnail image for Thumbnail image for Q1 ProductionisStreamlining Clearance & Approval Processes by Thoroughly Understanding Implications of New FDA Guidances Surrounding 510(K) Device Modifications & Refuse-to-Accept Policy while Successfully Addressing Inconsistency in Reviewer Feedback

The medical device regulatory landscape continues to evolve as new guidances are released by FDA, & global regulatory bodies are emerging or developing stricter guidelines for product approvals. Regulatory affairs executives in the device industry must stay abreast of these changing regulations in order to implement forward-thinking strategies for streamlining product approvals, & ultimately bring new & innovative products to market that will advance healthcare outcomes. The 3rd Annual Medical Device Regulatory Clearance & Approval Conference will build off the success from previous meetings by bringing together perspectives & insights from leading regulatory affairs professionals & innovative device manufacturers on how to ensure positive regulatory clearance & approval decisions in the US & internationally.

This two day conference will take place in Alexandria, Virginia on October 28-29, 2013. Attendees of this year’s program will have an exclusive opportunity to gather the latest insights into new & evolving FDA guidances & the implications for device manufacturers. Two key guidances of concern for regulatory affairs executives include the re-release of the 510(K) Device Modifications guidance along with the recent Refuse-to-Accept Policy. Presentations will also address internal strategies for tackling inconsistencies amongst FDA reviewer feedback & an increase in data requirements Continue reading

boywithflu.jpgOn June 28, 2013, FDA approved GlaxoSmithKline Biologicals’ (“GSK”) Flulaval® Quadrivalent (Influenza Virus Vaccine) for the 2013-2014 flu season. Flulaval® Quadrivalent protects against two influenza-A virus strains and two influenza-B virus strains and is approved for ages 3 and older. This season is the first time that vaccines protecting against more than three influenza strains will be commercially available. The other quadrivalent vaccines that are currently available include: Astrazeneca/Medimmune’s FluMist® Quadrivalent, GSK’s Fluarix Quadrivalent, and Sanofi’s Fluzone® Quadrivalent.

Seasonal flu is caused by either type-A influenza strains or type-B influenza strains. Each year, the World Health Organization recommends that vaccines address the two type-A strains that are most common in humans, and the type-B strain that is expected to be the most predominant in the upcoming flu season. Vaccines that protect against three influenza strains are referred to as trivalent vaccines. “Trivalent influenza vaccines have helped protect millions of people against flu, but in six of the last 11 flu seasons, the predominant circulating influenza B strain was not the strain that public health authorities selected,” said Dr. Leonard Friedland, V.P. and Head, GSK North America Vaccines Clinical Development and Medical Affairs. Dr. Friedland also noted that, “Trivalent vaccines do reduce influenza risk even in years when a vaccine strain-mismatch occurs, though quadrivalent influenza vaccines are the important next step in broadening strain coverage.” For the 2013-2014 flu season, the World Health Organization recommended protection against a second type-B influenza strain.

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Written by Julie E. Kurzrok

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Three other quadrivalent vaccines have been approved by FDA for the 2013-14 flu season. Fluarix Quadrivalent is an intramuscular vaccine that requires 1-2 doses depending on a person’s age and/or vaccination history. It is approved for ages 3 and older. FluMist® Quadrivalent is a live, attenuated vaccine that is administered via intra-nasal spray in 1-2 doses depending on a person’s age and/or vaccination history. It is approved for ages between 2 and 49 years. Fluzone® Quadrivalent is an intramuscular vaccine that requires 1-2 doses depending on a person’s age and/or vaccination history. It is approved for ages 6 months and older.
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Thumbnail image for DEA Badge.jpgOn August 19, Eisai Incorporated (“Eisai”) filed a Writ of Mandamus to Redress Unreasonable Delay by the Drug Enforcement Administration (“Writ”) to compel the Drug Enforcement Agency (“DEA”) to issue a Notice of Proposed Rulemaking (“NPRM”) within ten days of the Writ and otherwise expedite its drug scheduling for Fycompa® (perampanel). According to Eisai, DEA’s failure to initiate the scheduling of Fycompa® almost seven months after receiving a scheduling recommendation from the Assistant Secretary for Health (“ASH”) “constitutes unreasonable and egregious delay warranting mandamus.” In Eisai’s opinion, mandamus is warranted because: “(i) many thousands of patients who may benefit from the drug cannot obtain it, (ii) the drug’s sponsor is unable to benefit from FDA’s approval [of Fycompa®, and (iii) the burden on DEA of scheduling this drug is very small.”

Eisai’s Writ explained the process where FDA sends its drug scheduling recommendation through the ASH to DEA to initiate a scheduling proceeding “within a reasonable time” to permit the drug to be marketed with the appropriate scheduling safeguards. Under the Controlled Substances Act (“CSA”), if a drug has the potential for abuse, it must be subject to DEA scheduling, which considers “the eight-factor analysis” indicative of abuse potential and places the drug in one of five drug schedules. Schedule II is the most restrictive category where the drug is still accepted to have an accepted medical use, and Schedule V is the least restrictive schedule with an accepted medical use yet a low potential for abuse, physical dependence, or psychological dependence relative to other drugs or substances in Schedule IV.

The CSA permits DEA to add, change, or delete a substance’s schedule at any time by FDA/Health and Human Services or by petition from ay interested person or entity. The process that Eisai referred to, however, is the initial approval of a new chemical entity (“NCE”), where there was previously no schedule for the drug substance, and FDA recommends that a drug be scheduled prior to marketing. Although FDA lacks the direct authority to restrict marketing of products with pending DEA scheduling orders, FDA includes FDA Form 356h as a cover sheet for all new drug applications (“NDAs”) with a statement that the sponsor will not market until DEA makes a final scheduling decision. In the past, sponsors have honored these commitments to wait for a final scheduling decision before marketing their FDA-approved NDAs. Sponsors have waited despite FDA starting the clock for the five-year NCE exclusivity from the date of FDA’s approval letter rather than the final DEA scheduling, i.e., losing exclusive marketing time.
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