October 1, 2013

FLH's Brian Malkin Quoted in "The Pink Sheet" Article on GDUFA Update

Thumbnail image for drugmoney.jpegOn September 30, 2013, FLH Partner Brian J. Malkin was quoted in an article in "The Pink Sheet" entitled "GDUFA Plus One: Stakeholders, FDA Confident As Review Goals Near" (subscription or article fee required). The article summarized progress since the Generic Drug User Fee Act ("GDUFA") was enacted last year. GDUFA permitted FDA to collect fees from generic drug applicants and holders of drug master files ("DMFs") in exchange for certain efficiency enhancements and the promise for considerably shorter review times for abbreviated new drug applications ("ANDAs") in coming years. While FDA does not have to meet any ANDA review deadlines this year, starting with applications received from the fiscal year beginning October 1, 2014, FDA will need to review 60% within 15 months, then 75% within 15 months the following fiscal year, and 90% within 10 months of submission the next year.

FDA has reported progress with collecting fees, hiring new reviewers, and beginning to train these reviewers, as well as making a dent in the ANDA backlog. Regarding fees, FDA reported collecting $255 million collected in fiscal year 2013, about $44 million less than the target. GDUFA required FDA to hire 231 new employees in fiscal year 2013 and on September 11, 2013, FDA said it had hired 234 GDUFA-tagged employees, which FDA is in the process of training. FDA also has reported that it has reviewed about 40% of the application backlog since GDUFA went into effect and has conducted completeness assessments for about 900 DMFs. At the same time, however, review times have remained at a mean of 30+ months and have appeared to now be even longer. FDA has attributed part of this to the need to train new reviewers, which takes seasoned reviewers away from ANDA reviews, with the new reviewers not up to speed yet. Malkin was quoted in two sections on early improvement and budget sequesteration. Excerpts from the full quotations in the article include, for example:

There also does not appear to be much evidence that inspection parity is evolving. Brian Malkin, an attorney at Frommer, Lawrence and Haug, said there continue to be delays getting facilities reviewed and approved for first-to-file generic applicants.

. . .

Budget sequestration may have hindered some implementation efforts, but Malkin said ultimately the changes taking place at FDA were necessary to improve its generic drug systems.

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September 27, 2013

Strategic Scientific Business Tactics Explored at MassBio Forum in Cambridge

biotechnology.jpgOn September 26, the Massachusetts Biotechnology Council ("MassBio") hosted the fourth part of its "Adventures in Biotech" Forum series entitled, "Executing the Dream II: Eyes on the Price - Strategic Science Tactics & the Pursuit of Business Objectives" . The purpose of this Forum was to discuss ways that scientific strategy may be worked into the philosophy of a new company, how the scientific strategy can propel the growth of the company, and how the scientific strategy may change over time as a result of that growth. The speakers included Birgit Schoeberl, Vice President, Early Stage Discovery, Merrimack Pharmaceuticals ("Merrimack"); Muthiah Manoharan, Ph.D., Senior Vice President Drug Discovery, Alnylam Pharmaceuticals ("Alnylam"); Laurence Reid, Ph.D., Senior Vice President, Chief Business Officer, Alnylam; and Steven Tregay, Ph.D., Founder, President and Chief Executive Officer, Forma Therapeutics ("Forma").

Each of the speakers had a different approach as to how they incorporated their scientific strategy into their business. Tregay, for example, described Forma as a "sustainable research and development discovery engine" focused on oncology therapies that can screen 30-40 individual (not combinational) targets a year using an iterative process that includes: computational and medicinal chemistry, parallel synthesis, X-ray crystallography and relevant biology studies. According to Tregay, Forma's science permits it to mitigate risk by running in parallel a large number of discovery programs while continuously assessing the molecules, prioritizing targets for their pipeline at the appropriate scale, and maintaining communication between all scientists, and project teams. As part of its strategy, Forma first goes broad to investigate a cancer target technology and then more specific as aspects of that technology are validated and ready for candidate screening. Integral in Forma's strategy is forming partnerships with companies interested in screening many potential cancer candidates quickly rather than few candidates exhaustively, where it already has formed partnerships with Celgene, Boehringer Ingelheim, Genentech, and Johnson & Johnson, as well as some research universities.

Reid explained that Alnylam's focus has been on building its platform technology on ribonucleic acid interference ("RNAi"), a natural mechanism for silencing specific genes. RNAi is a biological process in which ribonucleic acid ("RNA") molecules inhibit gene expression, typically by causing the destruction of specific messenger RNA ("mRNA") molecules. RNAi has gone by other names in the past, including co-suppression, post transcriptional gene silencing ("PTGS"), and quelling. Genes provide cells with the instructions for making proteins, and abnormal proteins are frequently the cause of human disease. The theory behind RNAi therapy, therefore, is to use double-stranded RND ("dsRNA") to silence certain genes involved in the diseased state and reduce the occurrence of the associated disease. Scientists at Alnylam developed a new strategy to trigger RNAi in mammalian cells using relatively-small dsRNAs--long enough to induce RNAi, but small enough to avoid inducing an immune response--to permit RNAi to be considered as a new therapeutic strategy.

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September 26, 2013

Smartphone Health App Guidance Issued by FDA

medical app.pngOn September 25, 2013, FDA issued a final Guidance for Industry and Food and Drug Administration Staff entitled, "Mobile Medical Applications". This Guidance discusses FDA's intention to oversee the use of mobile applications ("apps") that qualify as medical devices and that pose a risk to the user if they do not function as intended. These "mobile medical apps" meet the definition of a medical device, and are either intended "to be used as an accessory to a regulated medical device; or transform a mobile platform into a regulated medical device." Section 201(h) of the Federal Food, Drug and Cosmetic Act ("FD&C Act") defines a device as

[A]n instrument, apparatus, implement, machine, contrivance, implant, in vitro reagent, or other similar or related article, including any component, part, or accessory, which is . . . [I]ntended for use in the diagnosis of disease or other conditions, or in the cure, mitigation, treatment, or prevention of disease, in man or other animals, or . . . [I]ntended to affect the structure or any function of the body of man or other animals, and which does not achieve its primary intended purposes through chemical action within or on the body of man or other animals and which is not dependent upon being metabolized for the achievement of its primary intended purposes.

FDA places mobile medical apps in the same category of risk as currently regulated devices and intends to regulate them in the same way. The Guidance aims to assist manufacturers in determining whether a product qualifies as a mobile medical app and, if so, provides FDA's regulatory requirements. FDA sets forth three types of mobile medical apps that it intends to apply regulatory oversight to:


  1. Mobile apps that connect to medical devices and are extensions of these devices that control, display, store, analyze, or transmit data from the medical device.

    For example: an app that controls the delivery of insulin by transmitting signals to an insulin pump.


  2. Mobile apps that transform the mobile platform into a regulated medical device.

  3. For example: an app that attaches electrocardiogram electrodes to a mobile platform to measure, store, and display electrocardiogram signals.

  4. Mobile apps (software) that perform patient-specific analyses and then provide patient-specific diagnoses or treatment recommendations.

  5. For example: an app that calculates radiation dosages or creates dosage plans for radiation therapy

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September 24, 2013

Biosimilars Naming Policy at Issue in Recent GPhA Citizen Petition

Thumbnail image for Thumbnail image for Thumbnail image for Thumbnail image for Thumbnail image for gpha-headerLogo.gifOn September 17, 2013, the Generic Pharmaceutical Association ("GPhA") formally jumped into the biosimilars naming fray by recently submitting a Citizen Petition to FDA on the issue. GPhA's Petition argues that a biologic approved under Section 351(k) of the Biologics Price Competition and Innovation Act of 2010 ("BPCIA") should share the same International Non-Proprietary Naming ("INN") system name as the reference protein product ("RPP"). GPhA's position stands in sharp contrast to a position voiced by the Biotechnology Industry Organization ("BIO") and Pharmaceutical Research and Manufacturers Association ("PhRMA"), which was outlined in a letter addressed to Margaret Hamburg last year. The BIO/PhRMA letter asserts that biosimilars are merely similar to--but not the same as--an RPP, and therefore each product should be assigned a unique INN. Requiring a unique INN will very likely require biosimilar applicants to market and detail biosimilar products themselves (instead of relying on the automatic substitution which occurs for generic small molecule drugs in most states).

The BPCIA does not provide a naming convention for biosimilar products. GPhA argues that FDA's experience with biologic products that undergo post-approval manufacturing changes should serve as an exemplar for biosimilars. For example, GPhA argues that FDA applies "conceptually the same standard" to approving biologic manufacturing changes as the "highly similar" standard required by the BPCIA. And for biologic manufacturing changes, FDA allows the RPP product to maintain the same INN as prior to the manufacturing change. Thus, GPhA argues that FDA should apply its naming standard for manufacturing changes to biosimilars as well. If FDA determines that biosimilars require different INN names than the RPP, then GPhA argues that FDA will be forced to require "new INNs for any product, originator or biosimilar, which undergoes a manufacturing change using comparability."

GPhA also addressed concerns that shared RPP and biosimilar INNs would interfere with product tracking. GPhA counters that notwithstanding a shared INN, biosimilar product labeling will contain sufficient information for tracking, such as manufacturer name, brand name, lot number, and NDC code. What is more, the results of a survey commissioned by GPhA reveal that "[h]ealth professionals typically report multiple elements whenever possible and include only the INN as the sole data point less than 30% of the time." On the other hand, GPhA argued that requiring a unique INN for each biosimilar could jeopardize patient safety by resulting in: (1) prescribing errors by clinicians, such as the possibility of double-dosing, (2) untreated patients due to compromised access, and (3) a failure to pick up safety issues that would only be apparent in aggregated data.

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September 23, 2013

505(b)(2) NDA RLD and Impurities Explained in Petition Response

Thumbnail image for ANDA drugs.jpgOn September 18, 2013, FDA provided a response to two citizen petitions filed by David B. Clissold, Director, Hyman, Phelps & McNamara P.C. ("Clissold's Petitions"). Clissold's Petitions requested that FDA refuse to file any new drug application ("NDA") filed under section 505(b)(2) of the Federal Food, Drug, and Cosmetic Act ("FD&C Act") (hereafter, "505(b)(2) NDA") seeking approval of a buprenorphine/naloxone drug product in the form of a polymer film for oral mucosal membrane absorption unless the application referenced NDA No. 22-410 for Suboxone® sublingual film (buprenorphine hydrochloride / naloxone hydrochloride) ("Suboxone Film"). As a quick summary, a 505(b)(2) NDA is not identical (i.e., generic) to a previously-approved drug. Instead, a 505(b)(2) NDA contains full reports of safety and effectiveness where at least some of the information required for approval came from studies that the applicant did not conduct/sponsor or have a right to reference. Clissold's Petitions also asked that FDA refuse to approve such application unless any genotoxic or potentially genotoxic impurity associated with naloxone are appropriately limited. FDA granted and denied in part Clissold's Petitions following a review of the Petitions, a supplemental letter from Clissold, and additional filed comments from a 505(b)(2) NDA applicant for buprenorphine/naloxone buccal film.

Following a discussion of the 505(b)(2) NDA approval framework, FDA agreed that it could refuse to file certain 505(b)(2) NDAs that did not "on its face contain required information" yet declined to so hold for the buprenorphine/naloxone product in question, if it failed to reference Suboxone Film. Like Clissold, FDA referenced its 2004 citizen petition response to Abbott Laboratories and Laboratories Fournier regarding fenofibrate ("Fenofibrate Petition"). In FDA's response to the Fenofibrate Petition FDA explained that when there is no pharmaceutical equivalent to a listed drug, an applicant should submit its 505(b)(2) NDA referencing the most similar product to reduce the amount of additional data to submit for approval.

FDA further explained in its response to Clissold's Petitions, however, that while an applicant's failure to reference the most similar product would not be a basis for a refusal to file, it could become an approval issue, if the applicant cited to an inappropriate reference product. In essence, an applicant's "approach to its development program" should be the guide to the appropriate reference product. And if there were a pharmaceutically-equivalent product, then the 505(b)(2) NDA applicant should identify such product and file the appropriate patent certifications. This latter situation generally describes a situation where a 505(b)(2) NDA may be submitted instead of an abbreviated new drug application ("ANDA") following approval of a suitability petition for certain allowed changes to previously-approved NDA products. Some of the situations where a suitability petition may be submitted are for ANDAs that differ from the listed drug in route of administration, dosage form, strength, or if it contains a different active ingredient in a combination product.

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September 20, 2013

HHS Adverse Event Plan Mentions FDA but Focuses on CMS as a Central Actor

HHSOn September 4, 2013, the Department of Health and Human Services ("HHS") released a report entitled "National Action Plan for Adverse Event Prevention" ("Plan"). The 176-page report purports to "engage all stakeholders in a coordinated, aligned, multi-sector, and health literate effort to reduce ADEs [adverse drug events] that are most common, clinically significant, preventable, and measurable." For this effort, the Plan focused on the intended end-users, "policymakers, health care professionals, public and private sector organizations, and communities who can organize and take action toward preventing high-priority ADEs." The high priority targets identified to prevent ADEs are the drug classes of anticoagulants, diabetes agents, and opioids. The four-pronged approach includes: surveillance, prevention, incentives and oversight, and research.

ADEs may occur in both inpatient (hospital) and outpatient and long-term settings. According to statistics cited in the Plan, ADEs account for about two million hospital stays annually and prolong hospital stays by about 1.7 to 4.6 days. ADEs in outpatient settings account for reportedly over 3.5 million emergency department visits, resulting in 125,000 hospital admissions each year.

The Plan acknowledges that a certain amount of passive (voluntary) reporting of ADEs comes via FDA's Adverse Event Reporting System ("FAERS") as well as FDA's Sentinel Initiative that monitors over 125 million lives but, the Plan says, "which do[es] not constitute a nationally representative sample, but for specific studies, FDA's Sentinel Initiative has the potential to access health records to confirm coded data or provide additional data." FDA's Sentinel Initiative was established in response to the FDA Amendments Act ("FDAAA") passed in 2007, which mandated that FDA establish an active surveillance system for monitoring drugs, using electronic data from healthcare information holders. The goal of the Sentinel Initiative is a new active surveillance system that could be used to monitor all FDA-regulated products. In particular, the Sentinel System draws on existing automated healthcare data from multiple sources to actively monitor the safety of medical products continuously and in real time.

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September 19, 2013

House Compounding Bill Seeks to Provide Clarity and Balance Between FDA and State Boards of Pharmacy Oversight

pharmacymortarpestle.pngLast week, Representatives Morgan Griffith (R-Virginia), Diana DeGette (D-Colorado), and Gene Green (D-Texas) introduced in the House compounding legislation entitled the "Compounding Clarity Act of 2013" (H.R. 3089) that could give FDA additional official authority under the Federal Food, Drug, and Cosmetic Act ("FD&C Act") over compounding facilities. The Bill comes after almost a year after contaminated drugs from a Massachusetts compounding facility caused 64 people to die from fungal meningitis.

According to Green, "For the last several weeks, a bipartisan and bicameral group of lawmakers have been meeting to make sure we never relive the tragedy of the 2012 fungal meningitis outbreak that originated in a compounding pharmacy in Massachusetts." Griffith said that the bill would "prevent another [New England Compounding Center]-type outbreak from occurring and ensuring the quality and safety of all compounded drugs in the country."

The Bill would amend Section 503A of the FD&C Act with a new framework and standards for traditional compounding pharmacies and additional FDA oversight for large-scale compounding like the New England Compounding Center. The legislation would help remove the Constitutional concerns concerning advertising that had been raised in various court cases and had raised certain questions about FDA's regulatory authority over compounding.

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September 18, 2013

Sound Prediction Unpredictability Causes Angst to Lilly

canada.jpgEli Lilly ("Lilly") filed a CDN$500M North American Free Trade Agreement ("NAFTA") suit against the Canadian Government as a direct consequence of losing patent protection in Canada on two of its major drugs, Zyprexa® (olanzapine) and Straterra® (atomoxetine hydrochloride). The formal notice of arbitration came after it had failed to settle by negotiation the dispute it lodged in June 2013.

NAFTA obligates Canada to grant patents for inventions that are new, non-obvious, and useful. Lilley's position is that Canadian utility patentability rules are different than the Untied States and Europe. In the United States, the utility requirement is met by an assertion of a specific and substantial use, and in Europe the utility requirement is met by a use that is specified and "plausible." However, in Canada there can be the added requirement that if in the patent specification there is a "promise," for example, to treat a human disease with fewer side effects, then the utility is measured against that promise, and the patentee is required to prove that it has demonstrated or soundly predicted the promised result as of the date the patent was filed.

Lilly pointed out that Canada is a party to international treaties that require Member countries to offer a uniform level of substantive patent protection on a non-discriminatory basis, and Lilly argued this sound prediction requirement is discriminatory. The Canadian courts have been applying this "promise doctrine" since around 2005 and have invalidated 19 pharmaceutical or biopharmaceutical patents for lack of utility under this doctrine between 2005 and 2012. This doctrine has been codified within the Canadian Intellectual Property Office. The Manual of Patent Office Practice describes the "promise of the patent" as follows:

Where the utility of an invention is self-evident to the person skilled in the art, and no particular promise has been made in regard to any advantages of the invention (e.g. if the invention was to simplify a known invention), the self-evident utility is sufficient to meet the required standard.

Where, however, the inventors promise that their invention will provide particular advantages (e.g. will do something better or more efficiently or will be useful for a previously unrecognized purpose) it is this utility that the invention must in fact have.

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September 16, 2013

Animal Food Additive Petition Guidance Issued by FDA

compound feed.pngOn September 11, 2013, FDA issued a draft Guidance entitled, "Recommendations for Preparation and Submission of Animal Food Additive Petitions." This Guidance provides the Center for Veterinary Medicine's ("CVM's") recommendations regarding information to be included in food additive petitions ("FAPs") for animal foods. FDA regulates food and substances added to food, some of which are "food additives."

A food additive is:

any substance the intended use of which results or may reasonably be expected to result, directly or indirectly, in its becoming a component of or otherwise affecting the characteristics of any food, unless the substance in Generally Recognized as Safe (GRAS) among qualified experts under the conditions of its intended use, or meets one of the other exemptions to the food additive definition (e.g., new animal drug, color additive, etc.).

To use a food additive in animal food, the additive must first be approved by FDA for such use. The Federal Food, Drug, and Cosmetic Act ("FD&C Act") sets forth a petition process to ensure that the use of a food additive in animal food is safe. The process is set forth in section 409 of the FD&C Act. Prior to initiating a petition, applicants should verify whether the additive is already approved, i.e., there is a regulation in place for the intended use of the substance in animal food.

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September 13, 2013

ANDA Labeling / USP Featured at GPhA/FDA Conference Part 2 of 2

ANDA drugs.jpgThis is a the second part of the blog on the Generic Pharmaceutical Association ("GPhA") / FDA / United States Pharmacopeia ("USP") ANDA Labeling Workshop/USP User Forum held in Bethesda, Maryland on September 11-12, 2013. Following Rudy Wu, Pham. D., M.P.H., Team, Leader, Labeling Branch, OGD, Scott Dallas, R.Ph., Labeling Reviewer, OGD, provided an overview of OGD's view of medication errors, which has built upon several reports by the Institute of Medicine in 1999 and 2006. FDA has been working with a Merck labeling initiative to see how products can be modified to be more easily distinguished in particular on the pharmacist's shelf. Generic drugs, just like their innovator counterparts, may be confused by similar trade dress or packaging, which should be a consideration when filing an application, Dallas noted. In addition, specialty packaging, such as blister packs or clear parenteral doses have been an issue, Dallas explained, where space for labeling is tight and often difficult to read for practitioners.

Carrie Lemley, OGD's only current Labeling Project Manager, described OGD's labeling review as a multidisciplinary process. Regarding products with mandated risk evaluation and mitigation strategies ("REMS"), Lemley said OGD is tracking FDA's process to standardize REMS (see related blogs here and here). In particular, if generic applicants are supposed to use a single, shared system for the elements to assure safe use ("ETASU"), FDA expects the RLD sponsor and generic drug applicants to work together to develop the single, shared program.

To date, FDA has only granted one waiver (buprenorphine) to permit both an RLD and shared generic REMS, but FDA contemplates that waivers will only be granted with well-rationalized reasons, i.e., more than an inability to get along. ANDA applicants, however, are not responsible for developing a communication plan or assessments for REMS but is expected to update its REMS in line with the RLD, e.g., if FDA with draws the REMS requirement, a generic applicant should also request to withdraw its REMS (The process is not automatic.) In response to questions about the waiver process, Lemley stated that there is no formal process but the elements to include in a waiver request are:

  1. Description of efforts to negotiate and decision makers,
  2. Justification for waiver including inability to work out issues regarding control or finances,
  3. Explanation how a waiver would affect everybody in that system and how two systems could co-exist instead of one,
  4. Accounting of cost issues for implementation, and
  5. Anticipation of the burden on the healthcare system and consumers for the separate systems.

Continue reading "ANDA Labeling / USP Featured at GPhA/FDA Conference Part 2 of 2" »

September 12, 2013

ANDA Labeling / USP Featured at GPhA/FDA Conference Part 1 of 2

ANDA drugs.jpgOn September 11-12, 2013, the Generic Pharmaceutical Association ("GPhA") in coordination with FDA and the United States Pharmacopeia ("USP") hosted an ANDA Labeling Workshop/USP User Forum in Bethesda, Maryland. The first day featured FDA speakers from FDA's Office of Generic Drugs ("OGD") who focus on labeling and filing/approval issues, and the second day featured speakers from USP.

Peter Rickman, M.S., Director, Division of Labeling and Program Support, OGD, kicked off the program, noting that OGD had a lot of challenges implanting the efficiency goals of the Generic Drug User Fee Act of 2012 ("GDUFA"), including their new 10-month review goals. Rickman stressed that for OGD to meet those goals, abbreviated new drug applications ("ANDAs") will need to be high quality, which is why FDA is spending time educating industry about quality.

Rudy Wu, Pham. D., M.P.H., Team, Leader, Labeling Branch, OGD, explained that labeling reviews can take longer when a consult is needed, i.e., checking with another FDA office for labeling acceptability, including the Office of Chief Counsel ("OCC"), Office of New Drugs ("OND"), surveillance, epidemiology, pediatric, and other centers. When a consult is requested, OGD must wait for the other entity to respond, which may create additional delays. Wu said there are many reasons why labeling reviews may take longer than expected: waiting for a final United States Pharmacopeia standard to issue or be met, standardizing the generic risk evaluation mitigation strategies ("REMS"), consults, citizen petitions, pending regulations or guidances, new clinical experience, patents and exclusivity may cause generic applicants to submit formulations that differ from the reference listed drug ("RLD) or include labeling carve-outs, and nomenclature differences. For example, regarding nomenclature, Wu said sometimes the RLD may use non-compendia-standard terms where the Orange Book uses another term, and FDA is concerned that both the RLD and the generic versions include labeling to ensure that pharmacists understand that they are substitutable for one another.

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September 11, 2013

Functional Foods and Dietary Ingredient Safety Considered at FDLI Conference

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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September 9, 2013

Clinical Data Management Innovation Conference

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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September 5, 2013

E-Cigarette Use Increase Among Teens Elevates Public Health Concern

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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August 30, 2013

FLH's Brian Malkin Quoted in InsideHealthPolicy Article on Call for Shared REMS Rulemaking

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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