By Karla L. Palmer – 

As reported here yesterday on the track and trace provisions, after many months of legislative maneuvering and various iterations emanating from both the House and Senate, the Senate passed without amendment and by voice vote H.R. 3204 – the “Drug Quality and Security Act.”  The Act removes the unconstitutional advertising and promotion provisions that for years plagued Section 503A of the Federal Food, Drug and Cosmetic Act; thus clarifying long-standing confusion concerning whether and where FDA could enforce Section 503A.  The law is effective upon enactment, and Section 503A will be enforceable nationwide. 

The Act’s Section 503B creates a new category of FDA registrant called “outsourcing facilities.”  Distinguished from compounders engaged in more traditional compounding for individual patients based on individual prescriptions, outsourcing facilities will be permitted to compound and ship interstate large volumes of sterile drugs without first obtaining individual prescriptions.  These hybrid compounders can pay a registration fee and voluntarily register with FDA, while those compounders that remain more “traditional” pharmacies will continue to be primarily regulated by state boards of pharmacy.

Outsourcing facilities will be subject to FDA oversight similar to drug manufacturers, including compliance with current good manufacturing practices.  In addition to registering with the Agency, these facilities must report to FDA every six months products that they compound, and must report adverse events.  Section 503B also provides FDA the resources and authority to conduct risk-based inspections.  In addition, the law requires FDA to list FDA-regulated outsourcing facilities on FDA’s website, requires detailed labeling on compounded drugs, and prohibits false and misleading advertising.  We have prepared a detailed cheat sheet on the provisions of Sections 503A and 503B. 

Hyman, Phelps & McNamara, P.C. is very pleased to announce that Larry K. Houck and Riëtte van Laack, PhD have been named Directors of the firm.  Mr. Houck’s practice area encompasses controlled substances and regulated chemicals as well as state licensing and registration compliance issues.  Mr. Houck worked in the Drug Enforcement Administration’s Office of Diversion Control for 15 years as both a Diversion Investigator and as a Coordinator in the Office of Diversion Control’s Liaison and Policy Section prior to joining the firm in 2001. 

Dr. van Laack focuses her practice primarily in the area of food regulation and OTC products.  She also has extensive field experience in the food science and technology industry, working as a researcher abroad and in the United States.  Prior to joining the firm, Dr.. van Laack worked, among other things, as a researcher with the Agricultural Research Service of the USDA and as a professor at the Department of Food Science and Technology at the University of Tennessee.

The American Conference Institute will be holding its inaugural forum on
current Good Manufacturing Practices (“cGMPs”) in Washington, D.C. from Thursday, January 23 to Friday, January 24, 2014.  A copy of the conference program can be obtained here.  Hyman, Phelps & McNamara, P.C.’s Douglas B. Farquhar will be presenting at the conference in a session titled “International Inspections: Preparing For Inspection of Overseas Manufacturing Facilities by FDA and Comparable Foreign Regulatory Authorities.”

The conference will include presentations from regulatory and legal experts on myriad topics, including presentations from several key government officials.  Howard R. Sklamberg, Director of FDA’s Office of Compliance in the Center for Drug Evaluation and Research, will discuss the Agency’s “Case for Quality” Initiative.   Annamarie Kempic, Deputy Chief Counsel for Litigation in FDA’s Office of Chief Counsel, will discuss cGMP Complaints, Consent Decrees, and Corporate Integrity Agreements.  In addition, Jeffrey Steger, the Assistant Director in the Consumer Protection Branch, Civil Division of the U.S. Department of Justice, will give a rundown of notable cGMP actions.

FDA Law Blog is a conference media partner.  As such, we can offer FDA Law Blog readers a special $200 discount off the current price tier.  The discount code is: FLB200.  We look forward to seeing you at the conference.

By Jessica A. Ritsick & William T. Koustas –

Over 25 years ago, the Prescription Drug Marketing Act ("PDMA") was passed.  The PDMA called for implementation of a national system to follow prescription drugs through the supply chain.  After years of talking about it (see here), and months of kicking the can down the road in Congress, it’s finally here: H.R. 3204, the Drug Quality and Security Act, which mandates a federal, interoperable electronic track-and-trace system, has arrived! 

Bills on both sides of Congress started getting traction back in April (see our previous post here).  As Spring turned to Summer, there was speculation that a bill could be passed by summer recess. Summer turned to Fall, and by this point, a bi-cameral, bi-partisan version of the bill emerged (see our previous post here).  The bill was passed by voice vote in the House at the end of September, and there was hope that the Senate would pass it by the end of the fiscal year.  Then, the government shutdown happened, and the bill took a back seat.  However, at long last, here we are: a federal law mandating an interoperable electronic track-and-trace system is now a reality!  The fully interoperable electronic track-and-trace system is set to become a reality in 10 years, but in the interim, there are deadlines to get all players in the supply chain up to speed so that in a decade, the interoperable system is ready to go.

From a brief review, it appears that the bill has passed in identical form to the bill we blogged about and outlined in September (see our summary here, and a U.S. Senate press release here).  It’s hard to believe, after years of haranguing, that this has become a reality, and it appears likely this bill will soon be signed into law.  As Fall gets colder, we’re warmed by knowing that if anything is frozen this Winter, for once, it won’t be track-and-trace. 

By Riëtte van Laack –

On November 7, 2013, the Food Safety and Inspection Service (FSIS) amended its prior label approval system regulations to expand the circumstances in which certain types of labels and labeling are generically approved and do not need specific FSIS approval. 

Under the final rule, companies need not submit the label for approval if the label bears all required mandatory labeling features and includes only claims that are defined in FSIS’s regulations, the Food Standards and Policy Book (with the exception of natural and negative claims), and allergen statements in compliance with the Food Allergen Labeling and Consumer Protection Act.

Labels that cannot be generically approved include temporary approvals, labels for export only that bear labeling deviations, religious exemption (e.g., Buddhist exemption), and labels bearing special statements and claims.  With the exception of the child-nutrition box, which is reviewed by the Agricultural Marketing Service, claims that have been reviewed by other Government agencies (e.g., organic claims and health claims) are considered special statements and claims. 

FSIS issued a guidance providing additional information regarding the final rule. The guidance includes a long list of examples of statements that are not eligible for generic approval  and a list of examples of claims that are eligible.

The final rule is intended to reduce the time for approval of labels that do not qualify for generic approval.  Although the Agency will continue to review all label applications, labels that do not qualify for generic approval will receive first priority for review.  Applications for labels that qualify for generic approval will receive lower priority and may take longer to be reviewed.

The final rule also consolidates the regulations regarding approval of labels for meat and poultry (9 C.F.R. §§ 317.4, 317.5, 381.132, 381.133) into a new single part, 9 C.F.R. Part 412.

The rule will become effective on January 6, 2014, and, unfortunately, will not provide any relief to those affected by the backlog that resulted from the government furlough in October 2013.

By Jessica A. Ritsick & William T. Koustas –

At this year’s Health Care Distribution Management Association (HDMA) annual track-and-trace conference, most minds were focused on one thing: the potential passage of H.R. 3204, the Drug Quality and Security Act, which would mandate a uniform, national, interoperable electronic track-and-trace system.  We’ve been following the evolution of this bill, which has seen more definitive traction in Congress in the past year than it has in the 25+ years since the passage of the Prescription Drug Marketing Act (PDMA), which requires a drug pedigree system be put in place (see our previous posts here, here, here, and here.)  Luckily, we haven’t been holding our breath, and neither were the conference attendees, because when the conference closed on November 13, 2013, H.R. 3204 was taken up, yet again, by the Senate, only to be again delayed by an unrelated amendment from Senator David Vitter (R-LA).

The conference provided a thorough overview of what all players in the prescription drug supply chain could expect should the bill become law.  It also provided food for thought about potential hiccups in the law’s implementation over the next 10 years.  Unlike Congress, however, at HDMA, it seemed like everyone was on the same page.  The general tenor in the room was that a national track-and-trace system was welcomed.  Virginia Herold, Executive Director of the California Board of Pharmacy, expressed to the group that California found the bill satisfactory, although the 10 year timeline was longer than it preferred.  Connie Jung, Acting Associate Director of Policy and Communications for FDA’s Office of Drug Security, Integrity, and Recalls, also expressed satisfaction with the bill, but also acknowledged that the work was just getting started.  Dr. Jung conveyed to the group that FDA has been actively ramping up its efforts and looking ahead to the new track-and-trace world, and acknowledged that the Agency is not in this alone; working with other players in the game is both welcomed and necessary to success. 

With fingers crossed, attendees looked ahead to the future of track-and-trace.  Panelists expressed that the national system will hopefully make it harder for bad actors to corrupt the integrity of the supply chain, as the current patchwork of state pedigree laws allows bad actors to shop around for more lenient states.  It is hoped that this bill will put everyone on a level playing field and reduce loopholes.  Moreover, once implemented, panelists expressed hope that the systems created under the bill could be leveraged in other prescription drug problem areas, such as with prescription pain medication abuse (e.g., pill mills, doctor shopping).  While many expressed that some of the deadlines in the bill might be unrealistic, there was general consensus that supply chain partners were ready to get to work making this long-held dream a reality.

On November 20th, the Food and Drug Law Institute ("FDLI") will present a webinar on the regulatory requirements that apply to health-related claims for foods.  Hyman, Phelps & McNamara, P.C.'s Ricardo Carvajal will discuss requirements applicable in the U.S.  Vicente Rodriguez, current president of the European Food Law Association, will discuss requirements applicable in the European Union.  The presenters will compare and contrast requirements applicable to nutrient content claims, health claims, structure/function claims.  Time will be provided for Q&A.  Additional information and registration is available here.

By Allyson B. Mullen – 

For many individuals, a diagnosis, be it life threatening or chronic, is scary.  However, the trial and error process that can follow the diagnosis in order to find a therapy (e.g., drug, device and/or biologic) that works best for the patient can be just as scary.  It would be wonderful if, at the time of diagnosis, or shortly thereafter, doctors could with a high degree of confidence identify what the best treatment was for that individual and avoid this process.  Many such personalized treatments are now being developed, and in the recent report “Paving the Way for Personalized Medicine – FDA’s Role in a New Era of Medical Product Development,” (the “Report”) [issued on October 30, 2013, FDA says it is preparing to address these new types of treatments from a regulatory perspective. Report at 2.

Personalized Medicine, sometimes also referred to as “precision medicine,” has been defined by the National Academy of Sciences as “the use of genomic, epigenomic, exposure and other data to define individual patterns of disease, potentially leading to better individual treatment.”  Id. at 6.  Personalized Medicine typically involves two medical products, a diagnostic test (a device) and a therapeutic.  Id. at 8.  The diagnostic is generally regulated as a medical device, and can include in vitro diagnostic assays or in vivo tests (e.g., diagnostic imaging).  Although drugs and biologics are the most obvious therapeutics where personalized medicine will be used, all types of regulated products can be therapeutics.  For example, recently three dimensional printing was used to create a personalized tracheal splint based on CT images of the patient’s airway and lungs.  Id. at 9. 

According to the Report, “the era of personalized medicine” has arrived:

• In 2011, one third of the new drugs approved had some type of genetic or biomarker data in the submission relative to efficacy, safety or pharmacokinetics;
• Since 2010, CBER has licensed seven new products which require careful matching of donors and recipients; and
• The number of submissions to CDRH’s Office of In Vitro Diagnostics and Radiological Health (OIR) involving personalized medicine has increased by more than an order or magnitude.  Id. at 54. 

The Report goes on to tout FDA and industry’s recent successes in this area.  Specifically, the Report highlights the approval of Kalydeco, the first drug to treat the underlying cause of Cystic Fibrosis, rather than the disease symptoms.  Id. at 3.  Kalydeco was an output of decades of work by the Cystic Fibrosis Foundation and Vertex Pharmaceuticals, the drug’s manufacturer.  Id.  The drug was approved in only approximately three months after its application was granted “priority review.”  Id.  FDA emphasizes that this success was a result of a “well-prepared submission, strong evidence, and a commitment on the part of all of the parties involved.”  Id. 

In achieving such a success, the Report discusses the historic and recent scientific, policy and organizational changes that FDA has made to address personalized medicine products.  Id. at 14–22.  The Report stresses that the primary challenge it needs to address related to personalized medicine is the science.  To that end, the Report enumerates a number of ways in which FDA says it is addressing the scientific challenge of personalized medicine, for example:

• Biomarker Qualification Program.  CDER is working with external scientists and clinicians to develop biomarkers with an aim of establishing a framework for encouraging development, identification and regulatory acceptance of biomarkers in drug development.
• MicroArray and Sequencing Quality Control Project.  National Center for Toxicological Research (NCTR) scientists are running this FDA-led project to “advance translational and regulatory sciences by assessing technical performance and practical utility of emerging molecular biomarker technologies for clinical application and safety evaluation.”
• Genomic Reference Library.  The National Institute of Standards and Technology (NIST) and OIR are working together to develop genomic reference material to be used in evaluating whole genome sequencing instruments.
• Clinical Trial Design and Methods.  FDA is generally working on refining clinical trial design and statistical analysis.  Specifically, the I-SPY 2 Trial, developed by the Biomarkers Consortium, which consists of FDA, the National Institute of Health (NIH), and the pharmaceutical industry, was launched in March 2010.  This trial uses an adaptive trial design to reduce the speed and cost of development for new drugs for women with high-risk breast cancer.  Id. 43–46.

However, FDA acknowledges that there are a number of other challenges that both it and industry face with respect to personalized medicine, including:

• Coordination of Multiple Products. As discussed above, personalized medicine involves two products, which raises a host of issues since each product is generally developed on its own time frame, by a different company, and each is likely subject to differing regulations (e.g., diagnostics as devices and therapeutics often as drugs and biologics and sometimes as devices);  Id. at 32–35.
• Regulation of Diagnostics.  Many of the diagnostic tests used in personalized medicine are in vitro diagnostic assays (IVDs), which can be commercialized to laboratories as a kit subject to FDA regulation as a device, or can be developed and used solely by a single laboratory as a laboratory developed test (LDT).  FDA’s efforts to regulate LDTs has been controversial (as discussed in our previous post here).  FDA has been developing a risk-based framework for regulating LDTs, although to date, nothing has been finalized. Id. at 30–32.
• Limited Understanding of Disease and Lack of Infrastructure.  With all of the new technologies, there is a mass of new data, but it is still unclear what it all means, and the infrastructure to “analyze, integrate, share, and mine” the data does not yet exist.  Id. at 56.
• Clinical Adoption of New Diagnostics.  Just as it takes FDA time to understand and accept new technology, clinicians have been slow to use new diagnostic tools, possibly due to how new the technology is, and the lack of tools to help the clinician in interpreting what the results of the tests mean.  Id. at 57.  In addition, although not mentioned in the Report, the lack of reimbursement for these new diagnostics is also a big impediment to their adoption by clinicians. 

Lastly, with all of the growth and excitement in this area, FDA says it wants to ensure that those individuals who do not have the characteristics to benefit from certain therapies are not forgotten and that all sub-classifications of disease are considered.  Id.

It is clear that advancement of Personalized Medicine through therapeutics and diagnostics is a high priority for FDA, as shown by a five-page table listing the various guidance documents that FDA has issued in this area.  Report at 24-28.  And FDA plans to issue more guidance documents in this area.  For example, CDRH’s Fiscal Year 2014 Proposed Guidance Development List includes several draft and final guidance documents related to personalized medicine, for example, a final guidance document for In Vitro Companion Diagnostic Devices, and a draft guidance for Direct to Consumer (DTC) Genetic Testing: IVDs. 78 Fed. Reg. 66746, 66746 (Nov. 6, 2013). 

In sum, there are many regulatory challenges that still face companies developing personalized therapies and diagnostics, and there is a long way for both industry and FDA to go before many of these products become realities.  There are also external factors that play a key role, such as reimbursement, health care reform, and commercial considerations.  However, the Report does describe steps FDA is prepared to take to address new therapies and technologies to help facilitate growth in the area of personalized medicine.

By Dara Katcher Levy –

A new Warning Letter issued by FDA’s Office of Prescription Drug Promotion (OPDP) suggests that FDA may want a new fight when it comes to the issue of that pesky First Amendment and the interplay with FDA-regulated products. 

In a November 8, 2013 Warning Letter, OPDP alleges that statements made by Aegerion Pharmacueticals’ CEO during broadcast interviews on a CNBC talk show, “Fast Money,” constitute evidence of a new, unapproved, intended use for its drug, Juxtapid (lomitapide) capsules.  These statements, OPDP alleges, misbrand Juxtapid, making its distribution a violation of the Federal Food, Drug, and Cosmetic Act.  

This is the first OPDP Warning Letter that takes issue with an initial broadcast of statements aimed at the financial community, rather than the re-distribution of these materials for purposes of product promotion or as part of a “media pitch” (see our previous post here).   

FDA did not cite any of the company’s marketing materials to support its allegation that Aegerion intended a new use for Juxtapid, rather, the focus is solely on the CEO’s statements made as part of the “Fast Money” interviews.  Further, OPDP did not cite the traditional statutory provisions relating to false or misleading promotional materials in its Warning Letter; the statutory violation alleged is that the drug is misbranded as its labeling fails to include adequate directions for the new intended use as expressed in statements made by the CEO.  Although OPDP makes mention in the Warning Letter that Aegerion’s CEO failed to include risk information as part of the interview, this is unrelated to OPDP’s misbranding allegations relating to the new intended use for the drug.

We are interested to see whether OPDP will be increasing its enforcement focus on investor-related materials and other materials intended for the financial community.    

By Jennifer M. Thomas –

The generic drug industry has waited with bated breath since, as we reported here and here, FDA signaled that it was “considering a regulatory change that would allow generic manufacturers, like brand-name manufacturers, to change their labeling in appropriate circumstances.”  See Amicus Brief of the United States at 15, n. 2, Mutual Pharm. Co., Inc. v. Bartlett, 133 S. Ct. 2466 (2013) (No. 12-142).  On Friday, November 8, 2013, the wait was over.

FDA’s Proposed Rule would allow generic manufacturers to independently update product labeling through the “changes being effected” (“CBE-0”) supplement process that is currently only available to branded drug manufacturers with respect to product safety labeling.  Under the Proposed Rule, generic manufacturers could unilaterally change their safety-related product labeling, and those changes could take effect simultaneous with the companies’ notification of FDA and of the branded drug manufacturer – no prior approval required.

The current regulatory scheme only permits generic manufacturers to use CBE-0 to update their labels in conformance with the branded drug (also called the Reference Listed Drug, or “RLD”) label.  See 21 C.F.R. § 314.150(b)(10).  Practically speaking, this means that the branded drug manufacturer must change its labels first, followed by the generics.  Most importantly, the Supreme Court has determined that generic manufacturers’ lack of independence with respect to drug safety labeling makes it impossible for them to comply with both Federal drug labeling requirements, and state tort law (failure to warn or design defect) requirements.  See PLIVA, Inc. v. Mensing, 131 S. Ct. 2567 (2011); Mutual Pharm. Co., Inc. v. Bartlett, 133 S. Ct. 2466 (2013) (reasoning that the only way to correct a design defect with respect to a drug that cannot be reformulated is through labeling).  Thus, state product liability suits based on use of generic drugs have generally been held preempted by Federal law.  Id.

While FDA’s stated purpose in proposing the new rule is to “speed the dissemination of new safety information about generic drugs to health professionals and patients,” (FDA Press Release), it is no mistake that the first whisperings of this rule appeared in a case involving generic preemption.  FDA’s admission that “[i]f this proposed regulatory change is adopted, it may eliminate the preemption of certain failure-to-warn claims with respect to generic drugs,” seems a ridiculous understatement.  If finalized, this rule would change the entire regulatory and liability landscape for generic drug manufacturers.

But does FDA have the authority to promulgate the Proposed Rule?  And if so, should it?  Given the serious questions surrounding it, this Proposed Rule seems as likely to go the way of the dodo as to ultimately be finalized.

Concerns about FDA’s statutory authority are unavoidable.  FDA acknowledges that its proposed new regulatory scheme would result in at least a temporary multiplicity of labels for the “same” drug, a result that the statute appears to prohibit except in enumerated circumstances.  See 21 U.S.C. § 355(j)(2)(A)(v).  Specifically, the statute requires applicants for generic drug approval to provide “information to show that the labeling proposed for the new drug is the same as the labeling approved for the listed drug . . . except for changes required because of difference approved under a [suitability petition], or because the new drug and the listed drug are produced or distributed by different manufacturers.”  Id.; see also id. at § 355(j)(2)(C).

FDA’s Federal Register notice wisely avoids addressing the statutory “sameness” point directly.  However, it does note that by waiting to actually approve a safety-related CBE-0 supplement until FDA can simultaneously approve a change in branded-drug labeling, the Agency “ensures that the approved labeling for a generic drug continues to be the same as the approved labeling of its RLD.” (emphasis supplied).  See Proposed Rule at 34.  FDA is also careful to point out that the statute requires a generic drug label to be identical to the branded drug “at the time of approval,” and that only FDA regulations have taken the position that generic drug labeling must maintain the same label as the branded drug throughout the lifecycle of the generic product.  Proposed Rule at 13.  A position the Agency now proposes to alter.

Assuming FDA has authority to issue the Proposed Rule, it will give patients an avenue for recovery from generic drug companies after suffering an injury.  But will it keep patients from harm in the first place?  The desirability of FDA’s Proposed Rule from a patient-safety perspective is certainly open to debate, and will be a point of serious contention in the coming months.  This is evidenced both by the Agency’s own admittedly changed position, and by the immediate and opposite reactions to the Proposed Rule.  See, e.g., Statement of the Generic Pharmaceutical Ass’n; Press Release: Harkin Welcomes Release of Proposed Rules to Protect Consumers Using Generic Drugs.  

FDA acknowledges its previously long-held view that the labeling of generic drugs must be identical to that of the listed drug in order to ensure patient safety, not least because a generic drug’s approval relies upon safety and efficacy studies of the listed drug.  See 57 Fed. Reg. 17,950, 17,961 (Apr. 28, 1992).  It also “acknowledges that there may be concerns about temporary differences in safety-related labeling for drugs that FDA has determined to be therapeutically equivalent.”  Proposed Rule at 18.  Nevertheless,  the Agency argues that the changing prescription drug landscape, in which 80% of the drugs dispensed are generic, has altered the risk-benefit balance between clarity and consistency on the one hand, and speedier access to safety information on the other.  Proposed Rule at 14.  FDA proposes to address the inevitable confusion regarding multiple versions of safety labeling through increased transparency – a website listing all of the pending CBE-0 supplements for safety-related labeling changes.  Proposed Rule at 19-20.  We anticipate that, particularly in the case of drug products for which there are multiple generic manufacturers, this website would be a virtual cacophony of labeling.

The comment period on FDA’s Proposed Rule will be open at least 60-days after its publication in the Federal Register – until January 12, 2014 – and likely longer.  The Docket No. is FDA-2013-N-0500. 

Hyman, Phelps & McNamara, P.C. is pleased to announce that James C. Shehan has joined the firm as Of Counsel.  Previously, Mr. Shehan served for 19 years as Novo Nordisk Inc.’s General Counsel and Corporate Vice President of Legal, Government and Quality.  His extensive experience will bolster the firm’s already deep expertise in, and inside knowledge of, the drug industry.  Specifically, Mr. Shehan’s work at the firm will focus on:

• Internal investigations and strategic handling of federal enforcement actions;
• Corporate compliance and GMPs;
• Hatch-Waxman and advertising litigation;
• Private and public transaction due diligence; and
• Drug development, biosimilars, and other areas essential to the drug industry.

At Novo Nordisk, Mr. Shehan was a part of an executive team that led one of the most successful healthcare companies in the United States.  During his years there, Novo Nordisk became the US market leader in diabetes, established other thriving therapeutic areas, went from ~ 200 employees to more than 5000, and grew sales from ~$100 million to more than $5.5 billion while achieving over 40 consecutive quarters of double-digit sales growth.

Mr. Shehan began as the sole member of the legal department and eventually managed a staff of 100.  His tenure included the approval of four blockbuster drugs, a multi-year GMP investigation, a Supreme Court Hatch-Waxman case, the successful defense of a Lanham Act false advertising challenge to the launch of a new biotech product, the partial spin-off of ZymoGenetics Inc. in what was at that time the largest private equity placement in history, and patent litigations related to human growth hormone, medical devices, and inhaled and injectable insulins.

Mr. Shehan also established Novo Nordisk’s compliance program and government affairs function.  In the latter role, he led Novo Nordisk’s efforts to shape the passage and implementation of the Affordable Care Act, particularly the provisions that allow for the first time in the US the approval of biosimilar drugs and the Sunshine provisions that require pharmaceutical and medical device companies to publicly report certain payments to physicians.  In the former role, he obtained extensive experience in the areas of health care fraud, off-label promotion and government drug price reporting and discounting.

Mr. Shehan has served on the boards of the Healthcare Institute of New Jersey, the National Association of Manufacturers and the Healthcare Leadership Council.  He was also for many years a member of the Law Section Executive Committee of the Pharmaceutical Research and Manufacturers of America and the General Counsel Committee of the Biotechnology Industry Organization.  He is Chairman of the Board of the American Friends of the Statens Museum for Kunst (Denmark’s national art gallery).

Prior to Novo Nordisk, Mr. Shehan spent five years as a regulatory attorney at Pfizer, where he worked on matters such as the approval and launch of Zithromax, Zoloft, and Procardia XL and the product liability litigation and regulatory issues stemming from the Bjork-Shiley heart valve.  Mr. Shehan began his career as a Regulatory Counsel in the Office of the Associate Commissioner of Health at FDA.  He is a recipient of FDA’s Award of Merit for his work on the implementation of the Hatch-Waxman Amendments.

Mr. Shehan is a graduate of Georgetown Law School and the Columbia University.  He is admitted to practice law in New York State.

By Etan J. Yeshua –

The Food and Drug Administration last week initiated a process that could prohibit the sale of partially hydrogenated oils (PHOs), as well as food products containing industrially manufactured PHOs, such as certain baked goods, microwave popcorn, frozen pizzas, frostings, and stick margarine.  Citing evidence that the trans fatty acids in PHOs provide no known benefit to human health and that any incremental increase in trans fat consumption increases the risk of coronary heart disease (CHD), FDA announced its tentative determination that food manufacturers should be prohibited from selling PHOs, or adding them to foods, without first obtaining FDA approval for their use.  The Agency is seeking comments on its tentative determination, including information about the costs that the move would impose on the food industry, and particularly the costs to small businesses (see here).  The deadline for submitting comments is January 7, 2014.

Current Regulatory Status of PHOs

With the exception of two oils that FDA says are not widely used (i.e., partially hydrogenated versions of rapeseed and menhaden oil), FDA maintains that it has never directly authorized the use of a PHO in food.  That is, FDA has never approved the use of a PHO as a food additive, affirmed it as generally recognized as safe (GRAS), or granted a prior sanction.  Instead, according to FDA, “commonly used PHOs… have been considered GRAS (through a GRAS self-determination) by the food industry for use in food at levels consistent with good manufacturing practice based on a history of use prior to 1958” – the year that the Food Additives Amendment to the Federal Food, Drug, and Cosmetic Act was passed.  With last week’s notice in the Federal Register, FDA announced that it does not believe there exists a “consensus of expert opinion regarding the safety of” PHOs.  If the announced “tentative determination” is finalized, food manufacturers would effectively be prohibited from selling PHOs without first obtaining FDA approval for a specific use of a specific oil in specific amounts as a food additive. 

Health Effects of Trans Fats

Despite what it described as a significant decrease in the average consumption of industrially produced trans fatty acids in the U.S., FDA stated that “[o]n the average day, at least eight Americans die as a result of the trans fats in partially hydrogenated oils” and that “[m]ost of these deaths could be prevented by removing industrially produced trans fats from the US food supply.”  FDA cited controlled trials and observational human studies on trans fats, as well as the opinions of expert review panels from the Institutes of Medicine, the American Heart Association, the American Dietetic Association, the World Health Organization, the Dietary Guidelines Advisory Committee, and the FDA Food Advisory Committee Nutrition Subcommittee, all of which purportedly concluded that “there is no threshold intake level for industrially-produced trans fat that would not increase an individual’s risk of CHD, or adverse effects on risk factors for CHD.”  FDA also cited evidence that the trans fats in PHOs may worsen insulin resistance, increase diabetes risk, and put fetuses and breastfeeding infants at higher risk of impaired growth.  Given these findings, FDA has tentatively determined that PHOs are not GRAS for any use in food.

FDA’s Cost-Benefit Analysis

The Agency believes that “the benefits of this action would be much higher than the costs,” although it noted that “in many cases we have very limited data to support our rough estimates.”  Taking into account the cost to industry of reformulating and relabeling products and substituting ingredients, as well as the cost to consumers of changing recipes, FDA estimated the cost of its proposal to be between $12 and $14 billion (net present value) over 20 years.  On the other hand, the 20-year net benefit for removing PHOs from the food supply – including the medical costs that would be avoided, as well as the monetary value of preventing deaths and illnesses (e.g., each fatal heart attack prevented is valued at about $1.76-million) – is estimated by FDA to be between $117 and $242 billion.

Request for Comments

Comments related to FDA’s announcement can be submitted with regard to any aspect of the Agency’s tentative determination, but FDA has specifically requested input with regard to certain issues, including, among others:

• Whether there are data to support other approaches to addressing the use of PHOs in food (e.g., setting a limit on the levels of trans fats in food);
• How long it would take manufacturers to reformulate food products to eliminate PHOs from the food supply;
• What FDA could do to reduce the burden on small businesses that would result from removal of PHOs from foods; and
• Whether there are products that cannot be reformulated.

An article published in the current edition of Regulatory Focus, the flagship publication of the Regulatory Affairs Professionals Society (RAPS), and authored by Hyman, Phelps & McNamara, P.C.’s Alexander J. Varond discusses the recent trends and developments in personalized medicine, including FDA’s current thinking and new challenges facing industry.  Despite the promising potential of personalized medicine, the field is still in its infancy and there is much uncertainty.  The article surveys key issues for sponsors, including the potential effect of next-generation sequencing technology on companion diagnostics, the importance of payers in the development of personalized therapies, and new regulatory pathways being proposed to ensure companion diagnostic reviews keep pace with breakthrough therapies.

The New York Academy of Sciences will present a conference on scientific and regulatory issues pertaining to nanomedicine on November 21.  The conference will feature speakers from the U.S. and abroad so as to provide domestic and international perspectives.  Hyman, Phelps & McNamara’s Ricardo Carvajal will participate in a panel discussion on acceleration of the development of nanomedicine.  Further information and registration information is available here.  FDA Law Blog readers can use the code NANOMED25 to receive 25% off the cost of registration.

By Kurt R. Karst –      

Earlier this week, sanofi-aventis U.S., LLC (“Sanofi”) filed a Complaint in the U.S. District Court for the District of Columbia against FDA in what appears to be a first-of-its-kind lawsuit.  Sanofi alleges that FDA’s decision to make public a copy of the labeling approved on October 11, 2013 under NDA No. 020468 for the Over-the-Counter (“OTC”) use of Nasacort Allergy 24 HR (“OTC NASACORT”) for the temporary relief of symptoms of hay fever or other respiratory allergies (nasal congestion, runny nose, sneezing, and itchy nose) in adults and children ages 2 years and older violates the Administrative Procedure Act (“APA”).   

Despite having approved a prior approval supplement (S-035) under NDA No. 020468 for the prescription-to-OTC use of NASACORT nearly a month ago, despite having received four Freedom of Information Act (“FOIA”) requests to release the labeling, and despite FDA policy, the Agency has failed to post on the CDER Internet Web Page (at Drugs@FDA) a copy of the approved labeling text. 

FDA procedures have called for the prompt publication of approval information on the CDER Internet Web Page.  For example, FDA Manual of Policies and Procedures (“MAPP”) 6020.8, titled “Action Packages for NDAs and Efficacy Supplements,” directs FDA staff to promptly compile and disseminate drug approval action packages.  In particular, MAPP 6020.8 states that FDA Document Room Staff are responsible for “[e]nsuring that three copies of the action package are made and distributed according to the procedures in MAPP 4520.1, Communicating Drug Approval Information, upon notification by the project manager that the application has been approved.”  MAPP 4520.1 is currently being updated and has been temporarily removed from FDA’s website; however, the most recent version of that MAPP stated the following policy:

Approved labeling text or final printed labeling for new drugs . . . will be made available on CDER’s Web Site and the CDER Fax-on-Demand system within the time frames specified in this MAPP, a period not to exceed three working days. [(emphasis added)]

The reason for FDA’s failure to timely post the OTC labeling along with the currently-posted approval letter for the NDA supplement was not entirely clear; however, there were suspicions that Sanofi was claiming proprietary rights to the OTC NASACORT labeling until Sanofi’s consumer healthcare division, Chattem, Inc., begins making the drug available next year (see here).  Those suspicions were confirmed with the filing of Sanofi’s lawsuit.  According to Sanofi, “FDA rejected Sanofi’s requests for confidentiality and advised Sanofi that it would post the approved labeling and packaging on FDA’s website on November 12, 2013.” 

Sanofi alleges that the OTC NASACORT labeling is protected from public disclosure under FOIA Exemption 4.  That exemption protects “trade secrets and commercial or financial information obtained from a person [that is] privileged or confidential.”  According to Sanofi:

Until Sanofi’s labeling and packaging material is publicly disclosed, it constitutes proprietary information, the disclosure of which would cause substantial completive harm to Sanofi.  Accordingly, the labeling and packaging information falls within Exemption 4 to the Freedom of Information Act and the Trade Secrets Act, 18 U.S.C. § 1905 until Sanofi chooses to make the labeling and packaging public in connection with the launch of the product.

So what’s all the hubbub really about?  Competition of course!  FDA did not grant Sanofi a period of 3-year new clinical investigation marketing exclusivity for the prescription-to-OTC switch of NASACORT.  So some might say that the company’s efforts to prevent publication of the OTC labeling is a lifecycle management tactic that provides a limited period of de facto marketing exclusivity. 

As Sanofi alleges in the Complaint:

Release of Sanofi’s approved labeling and packaging materials prior to its launch of the OTC version of Nasacort Allergy 24 HR will cause substantial competitive harm to Sanofi because it will provide generic manufacturers with advance knowledge of the labeling that they must match and thereby will enable them to launch their competing products sooner than would be the case if they must wait until Sanofi launches its product

Release of this information will also permit manufacturers of competing branded products to prepare advertising and promotion materials in advance of Sanofi’s launch of its OTC product.

The FDC Act requires that the labeling of a generic drug approved under Section 505(j) – whether for prescription or OTC use – be the same as the currently approved labeling of the Reference Listed Drug.  Indeed, FDA and the Office of Generic Drugs (“OGD”) have recognized in guidance the need to promptly make labeling changes to meet these legal obligations, stating in relevant part that:

OGD believes that prompt revision, submission to the Agency, and implementation of revised labeling are important to ensure the continued safe and effective use of generic drug products.  Because the regulations state that the labeling of the generic must be the same as the innovator, the revision should be made at the very earliest time possible.

Without access to approved labeling, however, generic drug sponsors may be unable to meet relevant legal and FDA obligations.  (FDA has approved a single ANDA for a generic version of the prescription version of NASACORT – ANDA No. 078104, approved on July 30, 2009.)   Prompt approval of an ANDA labeling supplement could result in the unusual situation where a generic version of a brand-name drug is available to consumers before the brand-name drug is available.

Sanofi requests that the court set aside FDA’s decision to make public the OTC NASACORT labeling as a violation of the APA, declare that FDA’s decision to make public the OTC NASACORT labeling because of the non-applicability of FOIA Exemption 4 violates the APA, and declare that the OTC NASACORT labeling falls within FOIA Exemption 4.  In the alternative, Sanofi requests that the court remand the matter to FDA for reconsideration, and preliminarily and permanently enjoin FDA from publicly disclosing the OTC NASACORT labeling until Sanofi launches the product.  (We'll update this post once Sanofi's injunction pleadings are available.)