FDA has recently challenged the use of wooden planks (shelving) to age certain cheeses, a practice that has been going on for centuries. The Agency is concerned that wood absorbs and retains certain bacteria, such as listeria, that can sicken cheese consumers. Many domestic and imported cheeses are aged on wood shelves, such as parmesan and certain blue varieties.

FDA’s Center for Food Safety communicated this concern to the New York State Agriculture Department, in response to an inquiry from the State about the issue. The inquiry was prompted by a warning letter and proposed consent decree sent by the Agency in October 2013 to Finger Lakes Farmstead Cheese Company in upstate New York, following an inspection of the company’s production facility that FDA said turned up listeria contamination. FDA took the position that wood shelving used to age cheese could be a hazardous substance, citing a longstanding regulation requiring cheesemaking equipment to be “adequately cleanable” and “properly maintained.”

An ensuing outcry from cheese producers, particularly New York and Vermont artisanal makers, caused FDA on June 11 to issue a “Clarification on Using Wood Shelving in Artisanal Cheesemaking.” The Agency backtracked somewhat, acknowledging that “the language used in this communication (to New York State) may have appeared more definitive than it should have,” and “FDA does not have data that directly associates these instances of contamination (past inspectional observations) with the use of wood shelving.” FDA stated that it “will engage with the artisanal community, state officials and others” to have an “open dialogue” about the issue.

Thumbnail image for Thumbnail image for 120px-Components_of_a_MiniCiggy_e-cigarette.jpgThe Food and Drug Administration introduced a proposed rule yesterday that would extend its existing authority over certain tobacco products. Under the proposed rule, FDA would now oversee electronic/e-cigarettes, cigars, pipe tobacco, nicotine gels, waterpipe/hookah tobacco, and dissolvables. These products would be added to the ones already under FDA’s authority–cigarettes, cigarette tobacco, roll-your-own tobacco, and smokeless tobacco.

In 2009, Congress passed the Family Smoking Prevention and Tobacco Control Act, which gave FDA the authority to regulate the manufacture, distribution, and marketing of “tobacco products” to protect public health. The statute defines “tobacco products” as “any product made or derived from tobacco that is intended for human consumption, including any component, part, or accessory of a tobacco product (except for raw materials other than tobacco used in manufacturing a component, part, or accessory of a tobacco product).” The Act specifically delineated cigarettes, cigarette tobacco, roll-your-own tobacco, and smokeless tobacco as products over which FDA had authority. But Congress also provided that FDA had authority over “any other tobacco product that the Secretary by regulation deems to be subject to this chapter.” Accordingly, through this proposed rule, FDA is “deeming” electronic/e-cigarettes, cigars, pipe tobacco, nicotine gels, waterpipe/hookah tobacco, and dissolvables to be “tobacco products” subject to FDA regulation. Under the rule, any future products that meet the statutory definition of “tobacco product” would also be deemed to be subject to FDA’s authority.
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Thumbnail image for Thumbnail image for Thumbnail image for Thumbnail image for gavelgold.jpgZogenix, Inc., the San Diego-based manufacturer of the extended-release hydrocodone drug Zohydro ER, has sued the Governor of Massachusetts in U.S. District Court in Boston to overturn as unconstitutional the state’s recent prohibition against prescribing and dispensing the medication.

Zohydro ER is the only FDA-approved hydrocodone drug indicated for daily, round-the-clock, long-term treatment of chronic pain for which other pain treatments are inadequate. The product, which was approved last year, is also the only available extended-release opioid drug containing hydrocodone alone, not combined with acetaminophen, which has been associated with liver damage.

The Governor of Massachusetts recently issued an “emergency declaration” establishing the ban, without consulting Zogenix, on the ground that a hydrocodone-only drug presents a greater risk of overdose and abuse than a hydrocodone combination drug. The ban would remain in place until “adequate measures are in place to safeguard against the potential for diversion, overdose and misuse.”
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functional foods.jpgFoodborne illness affects approximately forty-eight million Americans per year, according to recent data from the CDC. Consumers have heard news stories warning of nationwide food recalls. What additional steps can be taken to ensure food safety? The FDA Food Safety Modernization Act was designed to address that question. Included in Section 211 of that Act are new provisions related to a Reportable Food Registry system (RFR) for increasing the speed of investigation and action to address foodborne illness (this is separate from FDA’s recall program). Although FDA already had a public meeting in June 2011, the agency only received three comments, and believes it needs further input. So, on March 26, 2014, FDA published an advance notice of proposed rulemaking (ANPR) seeking public comment through June 9, 2014.

The proposal may require submission to FDA by a responsible party through the RFR of consumer-oriented information regarding a reportable food (information necessary to accurately identify whether a consumer possesses a reportable food) within twenty-four hours of discovery of an event. A “responsible party” is the person that submits a food facility registration related to the reportable food. A public health official may also submit a report, but not consumers. FDA would assess the information and publish a standardized one-page summary on its website for purposes of notifying consumers. FDA may require the responsible party to notify or provide contact information for upstream and downstream supply chain entities. Grocery stores that sold the reportable food would be required to prominently display that information within twenty-four hours of the FDA’s website posting, and for a period of 14 days. FDA is required to develop a list of acceptable conspicuous locations and manners for grocery stores to post the information.

“Consumer-oriented information” would include a description of the reportable food, production identification codes for the reportable food, contact information, and any other information for the consumer to identify the reportable food. “Reportable foods” are those “for which there is a reasonable probability that use of, or exposure to, such food will cause serious adverse health consequences or death to humans or animals.” The new provisions will also not apply to fruits and vegetables.
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Thumbnail image for Thumbnail image for Thumbnail image for Thumbnail image for Thumbnail image for Thumbnail image for FDA.bmpFDA issued a draft guidance on March 18, 2014 titled, “Bioavailability and Bioequivalence Studies Submitted in NDAs or INDs – General Considerations.” This draft guidance seeks to revise and update FDA’s March 2003 guidance titled, “Bioavailability and Bioequivalence Studies for Orally Administered Drug Products — General Considerations.” This document provided guidance for NDAs, INDs, and ANDAs. In December 2013, FDA issued a draft guidance that deal with these issues solely for ANDAs. This week’s draft guidance tackles the remaining portion of the subject matter in the 2003 guidance: NDAs and INDs. Like the draft guidance on ANDAs issued in last December, this March 2014 draft guidance should not surprise those familiar with FDA’s bioequivalence (“BE”) requirements; however, it helpfully clarifies and updates a number of long-standing Agency positions.

The instant draft guidance describes that BE documentation could be useful in the IND and NDA context to compare various formulations implicated at various stages of the application life-cycle. For example, BE studies may be useful in the pre-approval context to compare: (1) formulations used in various stages of clinical trials, (2) clinical trial formulations with formulations used in stability studies; (3) clinical trial formulations with proposed final formulations; and (4) product strength equivalence. In the post-approval context, BE studies are required by FDA under certain circumstances if the innovator makes changes to the formulation.

FDA’s draft guidance issued this week also covers methods to document bioavailability and bioequivalence. It is not unexpected that the draft guidance devotes a significant portion to pharmacokinetic studies, laying out considerations relevant to study size, population, moieties to be measured, and pharmacokinetic measures of system exposure, to name a few. The usage of partial measures of exposure has been heavily debated in the past and this draft guidance confirms that they can be used in certain situations. The draft guidance also states, “[t]he time to truncate the partial area should be related to a clinically relevant PD measure.” The draft guidance also covers in vitro tests with in vivo correlation, pharmacodynamic studies, comparative clinical studies, and in vitro studies. Further, the draft guidance provides considerations specific to dosage forms, such as solutions (and other solubilized dosage forms), immediate-release products, and modified-release products.
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foodlabel.JPGLast week, the Food and Drug Administration proposed an amendment to its labeling regulations for conventional foods and dietary supplements to update the nutrition information (e.g. the Nutrition Facts labels) on packaged foods/drinks. The updates would come from two proposed rules that are published in the Federal Register. The first–Food Labeling: Revision of the Nutrition and Supplement Facts Labels–addresses new scientific information and design changes; the second–Food Labeling: Serving Sizes of Foods That Can Reasonably Be Consumed at One-Eating Occasion; Dual-Column Labeling; Updating, Modifying, and Establishing Certain Reference Amounts Customarily Consumed; Serving Size for Breath Mints; and Technical Amendments–addresses serving sizes, labeling requirements based on package size, and other issues.

FDA has grouped the proposed changes into three categories: (1) Greater Understanding of Nutrition Science; (2) Updated Serving Sizes and Labeling Requirements; and (3) Refreshed Design. Below is a summary of the significant proposals for each category.

1. Greater Understanding of Nutrition Science

  • New labels must include information about “Added Sugars”
  • Updated “Daily Values” for certain nutrients, including sodium, dietary fiber and Vitamin D
  • Require listing of potassium, Vitamin D, calcium, and iron amounts
  • Permit listing of Vitamins A and C amounts
  • Remove “Calories from Fat”

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multipills.jpgOn February 21, 2014, FDA issued a Draft Guidance that will now permit a fixed combination drug product containing a new active ingredient plus a previously approved active ingredient to qualify for New Chemical Entity (NCE) exclusivity, thereby preventing the filing of generic drug applications referencing the combination product for a period of 5 years. (A fixed combination drug is one containing more than one active ingredient, each in a fixed amount).

FDA’s prior approach, in effect since 1994, had denied NCE exclusivity status to a fixed combination drug product that included an already-approved active ingredient. By virtue of the new Draft Guidance, the Agency is changing its interpretation of pertinent sections of the Federal Food, Drug, and Cosmetic Act and its own regulations. Going forward, FDA will determine NCE exclusivity by considering the newness of each drug substance (active ingredient) in a fixed combination drug product. If one active ingredient is new, NCE exclusivity can be awarded to the entire product.

As reasons for the change, FDA cites: (i) the emergence of combination drug treatment as a standard of care for serious diseases such as cancer, cardiovascular disease and infectious diseases (e.g., HIV), and (ii) the need to encourage the development of fixed combinations to treat these and other diseases, because particular combinations have been shown to improve treatment response, lower risk of resistance and lower rates of adverse events.
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TVad.pngYou can hardly watch television without seeing a prescription drug advertisement. Often the most memorable part of the advertisement is the required voiceover disclosing a long list of all the risks associated with taking the drug. The problem becomes deciphering which risks are actually the serious ones. FDA seeks to find out if that long disclosure of risks results in “reduced consumer comprehension, minimization of important risk information, and potentially, therapeutic noncompliance due to fear of side effects.”

On February 18, 2014, FDA issued a notice seeking comments about its proposed collection of information – “Disclosure Regarding Additional Risks in Direct-to-Consumer (DTC) Prescription Drug Television (TV) Advertisements (Ads).” FDA proposes to investigate the impact of limiting the risk disclosure in prescription drug television advertisements to only those that are “serious and actionable” plus an alert that there are other risks associated with the drug but which are not disclosed in the advertisement.

FDA would like to hear from you by April 21, 2014 about: whether you think its investigation is necessary “for the proper performance of FDA’s functions;” whether the information will have practical utility; the validity of the methodology and assumptions its investigation will use; how the quality, utility and clarity of the information collected can be enhanced; and how the collection of information can be less burdensome on respondents.
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leerink.pngOn February 12 and 13, 2014, Leerink Partners LLC (“Leerink”) held its annual Global Healthcare Conference at the Waldorf-Astoria Hotel in New York, New York. Each year the Conference includes emerging themes in healthcare, where Leerink’s equity analysts moderate discussions with MEDACorp specialists to provide unique and timely insights.

In addition to the company presentations, this year’s line up featured the following panels or keynote speakers with some observed comments or trends:

• Panel: The Future of Medical Devices in an Evolving Landscape: A Shifting Emphasis to Patient Monitoring and Customizable Solutions

  • Patients view surgeons that incorporate robotics in their practice as the better doctors, driving more surgeons to utilize them in their practice. As surgeons become more familiar with these devices, patients may have more options for surgical procedures and implants.
  • Larger companies are looking at controlling infections caused by implanted medical devices with special coatings–either anti-infectives or antibiotics, particularly for use in higher-risk patients. There is an increasing need, however, for implants to have built-in tools for monitoring the devices. But as medical devices become more complex, such as hip, knee, or total joint replacements, these devices will require preapproval marketing applications (“PMAs”) with clinical data rather than less costly and time-consuming 510(k)-type premarket clearance applications. Since PMAs cost companies more than 510(k) applications, these newer devices will cost third party payors and patients more.
  • Hospitals continue to be under a lot of pressure not to lose patients, so they may seek lower margins by having surgeons add anti-infective coatings or antibiotics rather than purchasing more costly versions with the coatings or by importing “generic” implants from other countries that may not be as rugged as the versions cleared for use in the U.S. FDA’s new unique device identifiers and improved monitoring, however, may reduce use of such imported devices with unclear pedigrees.

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On Sunday, February 16, BioCentury This Week television examined the policies surrounding the expected competition of innovator biologic products with biosimilar versions. Featured in the program were interviews with:

  • Geoffrey Eich, Executive Director of R&D Policy at Amgen Inc.
  • Craig Wheeler, President & CEO of Momenta Pharmaceuticals Inc.
  • Brian Malkin Partner at Frommer Lawrence & Haug LLP and former Regulatory Counsel in the Office of the FDA Commissioner and the Center for Drug Evaluation and Research

Links to the interviews may be found below:


Brian Malkin

BioCentury 02/16/14 Safety v. Competition


Geoffrey Eich

BioCentury 02/16/14 Brand-Name Confidence


Craig Wheeler

BioCentury 02/16/14 Substitution Confusion

BioCentury 02/16/14 Competing Interests