FDA Lawyers Blog

by Howard E. Rosenberg, Ph.D.

The European Commission has updated its proposals with regard to the product information available to patients. Unlike in the United States, pharmaceutical companies in Europe cannot advertise their wares direct to the public, nor can they make claims about a medicine without clearance from Health Authorities and even then only in acceptable formats. The Commission's initial 2008 proposals have been updated to incorporate the European Parliament's amendments, the emphasis being on the rights and interests of patients.

The European Commission's press release explains "that patients are increasingly interested in learning more about the medicines they take and want more of a say in how they are treated. At the same time, patients are confronted with a growing volume of information from various sources and often find it difficult to identify reliable information about medicines. The increased use of the internet over recent years makes the need for clarity even more important. Online information on medicines must be accurate and reliable."

Some key elements of the amended proposals are:

1. Only certain information on prescription-only medicines will be allowed, e.g., information on label and package leaflets, prices, pre-clinical tests and clinical trials of the medicine concerned and on the instructions for correct use.
2. Only certain channels of communication will be allowed for providing information, e.g. via officially registered internet websites or through printed information provided this has been specifically requested by members of the public.

by Scot Pittman

FDA has put forth significant efforts in trying to tweak its 510(k) device approval pathway, which has created discontent among medical device companies for many years. In its most recent attempt to improve the medical device approval process, FDA released draft guidelines "De Novo Classification Process (Evaluation of Automatic Class III Designation)" last Monday.

De Novo Guidance

A typical low- to moderate-risk medical device approval requires either FDA clearance of a premarket notification or approval of a 510(k) submission. 510(k) submissions require a demonstration that the new device is substantially equivalent to an already legally-marketed device. The De Novo Classification Process attempts to streamline device approval for low- to moderate-risk devices that have been classified as Class III because they cannot be shown to be substantially equivalent to any legally market devices. In addition, the guidance also describes a mechanism for obtaining timely input on the type of data necessary to support de novo classification of a suitable device. When this guidance is final, it will replace "New Section 513(f)(2) - Evaluation of Automatic Class III Designation, Guidance for Industry and CDRH Staff" (February 19, 1998).

by Fitz Beckwith Collings

Center for Food Safety, have asked FDA to bring its regulatory power to bear on genetically-engineered ("GE") foods to prevent economic fraud and consumer confusion. They seek several definitional changes in the Federal Food, Drug, and Cosmetic Act ("FD&C Act") and U.S. Code of Federal Regulations ("C.F.R."), as well as the institution of mandatory labeling for all GE foods.

Definitional Changes

First up is rescission of FDA's 1992 policy statement regarding the definition of a "material" production process under FD&C Act Section 201(n). The current definition turns on processes that a consumer can detect using his senses. Petitioners seek to define a production process as material "if it results in a change to a food at the molecular or genetic level because a significant share of consumers would find it relevant to their purchasing decisions." Changing the definition, they argue, is consistent with FDA's authority and a failure to change it would be arbitrary, capricious, or contrary to the law.

Next, petitioners request the inclusion of definitions for "genetic engineering" and "genetically engineered food." The definitions highlight petitioners' food safety argument. "Genetic engineering" means "a process that alters an organism at the molecular or cellular level by means that are not possible under natural conditions or processes," and specifically excludes established selection processes like breeding, conjugation, fermentation, hybridization, in vitro fertilization, and tissue culture.

by Erin A. Lawrence

On September 29, FDA added a supplement to the 2009 Food Code that addresses recommendations made at the 2010 Meeting of the Conference for Food Protection. The new supplement would require businesses in the food service industry to hire certified food protection managers. The supplement aims to mitigate risk factors that contribute to foodborne illnesses.

FDA's Food Code is a set of model food-safety regulations for keeping food safe at retail and food-service operations including restaurants, schools, and food stores. FDA guidelines are not mandatory, but are adopted by many states to delineate food safety standards. Food Codes are issued by FDA every four years. The next complete revision to the Food Code will be published in 2013.

Forty-nine states pattern their food safety codes after versions of the federal Model Food Code. Twenty-four states already require certified food protection managers. To become a certified food protection manager, an employee must complete an educational program that is approved by a Conference for Food Protection-recognized agency. Recognized agencies include the National Restaurant Association's ServSafe program, Prometric, and the National Registry of Food Safety Professionals. The supplement calls for "[a]t least one employee that has supervisory and management responsibility and the authority to direct and control food preparation and service shall be a certified food protection manager who has shown proficiency of required information through passing a test that is part of an accredited program. " The certified food protection manager would be responsible for: 1) developing and implementing the operating procedures required by the food code; 2) apprise employees about their obligation to report certain health conditions; 3) make sure that any food delivered after operating hours is done so in a way that does not create a food safety hazard; 4) mandate a proper clean-up plan for an employee or customer that has gotten physically ill; 5) educate employees regarding the guidelines of using bare hands with ready-to-eat foods and; 6) clarifying the guidelines for storage of meat and poultry.

In addition to the supplement, FDA also announced that it established a cooperative agreement with the National Association of County and City Health Officials ("NACCHO"). Under the agreement, FDA and NACCHO will promote the use of best practices by local authorities, develop tools to strengthen retail food safety oversight, and implement FDA's Voluntary National Retail Food Regulatory Program Standards for retail food regulatory programs.

by Brian Malkin

FDA Lawyers Blog is pleased to announce the arrival of its new mobile apps for iPhones and Android smartphones. FDA Lawyers Blog, key FDA news feeds, and a phone-ready HHS directory are now available in the applications developed for iPhones and Android phones. Both apps can be downloaded directly from the Apple App Store and the Android Market free of charge. In addition, FDA Lawyers Blog is in the process of optimizing its blog to make it more readable on your iPhone or Android smartphone. Some of those changes have been implemented already, and we will announce them once the final mobile style sheets are in place.

Since we went live last year, FDA Lawyers Blog has provided cutting-edge, social media optimization for its blog featuring FDA news and updates for FDA lawyers and other interested users. Our blog features links and feeds to Facebook, Twitter, and LinkedIn with various options to share our blogs, including Twitter "tweets" and Facebook "likes" for individual posts. FDA Lawyers Blog's mobile applications feature similar sharing options but now adds FDA news feeds and a phone-ready HHS directory to make calling FDA even easier on your Apple or Android smartphone. With these enhancements, FDA Lawyers Blog takes its blog to a new global level of accessibility and usefulness for professionals in the field of FDA law. Continue to watch for additional upgrades as we listen to your comments about what you need to be more productive with regard to FDA news and updates.

Along these lines, please let us know what you think about the iPhone and Android apps. We are in the process of creating additional functionality for both the applications and mobile versions of FDA Lawyers Blog and look forward to providing our readers with additional mobile features to access the FDA news and updates you need for now and in the future.

by Brian Malkin

On October 5, FDA's David T. Read, Regulatory Counsel, Office of Generic Drugs ("OGD"), Center for Drug Evaluation and Research, presented a snapshot of generic drug applications and approvals since the Hatch-Waxman Amendments and the challenges going forward.

Acknowledging that OGD has a backlog of over two thousand abbreviated new drug applications ("ANDA") with a median 27.88 month review cycle, Read cited to a number of factors contributing the problem. First, OGD needs more resources (i.e., reviewers) to get rid of the backlog, which may be helped by the promised Generic Drug User Fee Act ("GDUFA") once it becomes law. Read explained that 505(q) citizen petitions (petitions that FDA must respond to within 180 days because they interfere with generic drug approvals among other things) and products with increased complexity also contributed to the problem. Read cited FDA's response to the enoxaparin citizen petition as an example of the enormous drain on resources caused by complex issues (in that instance, tough questions of "sameness").

In addition to GDUFA, Read explained that other potential solutions could include the better prioritization of ANDAs, and increased communication of the need for higher quality ANDAs and generic products. Here, Read mentioned ongoing complaints about antiepileptic drugs where practitioners and others continued to complain breakthrough seizures occurring in brand-to-generic switches, generic-to-generic switches, and generic-to-brand switches. The problem, Read noted, was that the "data stinks": meaning that the complaint of breakthrough seizures is based on anecdotal data rather than well-controlled studies.

by Kyle Deighan

The year 2010 saw a record 178 reported drug shortages in the United States. According to various sources, that number has already reached nearly 200 this year. The shortages include cancer drugs, anesthesia drugs, and other critical medications, the U.S. Food and Drug Administration ("FDA") reports. These shortages lead to dire consequences for patients that rely on the drugs, prompting many, including FDA, to take notice.

More recently, FDA held a day-long hearing on September 26th that was attended by medical and consumer groups, researchers and industry representatives, seeking to identify the causes and effects of shortages and strategies to address the problem. In addition to various presentations on the current status of drug shortages, attendees discussed the impact of shortages from the public's perspective and the health care provider's prospective. One recommended solution required manufacturers to notify FDA of drugs expected to be in short supply within a six month period. Currently, FDA requires those companies that are the sole source of medically necessary drugs to notify FDA at least 6 months in advance if the product will be discontinued. However, those companies face no penalties if they do not do so. According to FDA, early notice will allow it to more effectively address and work to avoid a shortage. FDA was reportedly able to prevent 38 shortages in 2010 when manufacturers voluntarily reported potential supply disruptions.

by Andrew S. Wasson

Today FDA announced a plan to create a network of outside scientific experts who would assist the Center for Devices and Radiological Health ("CDRH"). While CDRH currently employs a scientific staff and solicits the advice of outside experts, FDA hopes that the proposed network will provide FDA with "rapid access to specific specialized knowledge about emerging technology." FDA announced a pilot program which will run from September 30, 2011 to December 30, 2011. FDA released draft standard operating procedures ("SOPs") which will be open for comment starting on October 6, 2011: Expert Utilization Standard Operating Procedure and Expert Enrollment Standard Operating Procedure.

The draft SOPs clearly state that the network of experts is not intended to supplant the current systems used by FDA. FDA explains that the Agency derives expertise from a number of external sources: (1) advisory committee meetings, (2) scientific literature and conferences, (3) public workshops attended by scientific experts, and (4) ad hoc interactions with other federal scientists outside of FDA. The documents state that questions to external experts as a part of this program "should be limited to those that are scientific and necessary for CDRH staff to effectively complete their work and are not suitable for using any of the existing mechanisms outlined above." The SOPs also clarify that the network of experts will not make give policy advice or make policy decisions. Rather, "network members will share their particular expertise on specific topics to help center staff form their own conclusions." FDA's goal is to allow FDA scientists to draw on expertise outside of the current pool in a time-sensitive fashion.

by Fitz Beckwith Collings

Eli Lilly recently expanded its two-year-old open innovation program--the Phenotypic Drug Discovery Initiative--to include three distinct components for testing promising new drugs. The first component, PD(2), screens molecules submitted by independent researchers in the hope of identifying compounds for treatment that have novel mechanisms of action or operative in novel pathways. Lilly identifies several strategic areas of interest, including endocrine and cardiovascular systems, oncology, and neuroscience. The second component, TD(2), screens molecules that may interact with known disease targets. The third component screens molecules that may act against multi-drug resistant tuberculosis.

Lilly's open innovation initiative aims to crowd-source pharmaceutical development, in the hope that finding the medicines of the future could be as easy as finding a few red balloons. To participate, scientists upload conforming molecules to openinnovation.Lilly.com, and Lilly provides a comprehensive testing report. Scientists can then use advanced computational tools on Lilly's website to interact with the data.

In exchange for testing the molecules, Lilly gains the right of first negotiation for a collaborative or licensing agreement with the scientist. The scientist retains all other intellectual property rights, and the ability to publish and disseminate the data freely if no agreement is reached. Furthermore, if the scientist has identified a compound for tuberculosis, the scientist may elect to proceed down a non-profit pathway of drug development. Similar programs have been created by GlaxoSmithKline (for medicines to treat third-world diseases like malaria) and Sanofi (for hearing-loss treatments).

By Andrew S. Wasson

Multiple sources indicate that FDA is close to releasing an initial draft guidance on biosimilar products. Last Friday, Reuters reported that Janice Soreth, deputy director of the FDA's Europe office in London, stated that FDA might release the guidance "as early as the next few weeks, maybe even days." Soreth made the comments at Windhover's Pharmaceutical Strategic Alliances Conference in New York. Soreth's comments are consistent with BioCentury's September 22nd report that CDER director Janet Woodcock stated that the guidance would be issued "promptly."

It is clear that FDA has been steadily working toward a biosimilars draft guidance. After a long period of radio silence, in August the New England Journal of Medicine published an article titled "Developing the Nation's Biosimilar's Program" co-authored by FDA employees, including CDER director Janet Woodcock. We reported on that article here. Most commentators believe that FDA's upcoming guidance will hew closely to the principles set out in August's NEJM article.

In particular, FDA will likely allow itself a large amount of flexibility in determining the requirements for the approval of a biosimilar application, including the types of clinical and/or analytical studies necessary. Agency flexibility is particularly critical here because (1) biological products vary significantly in terms of complexity and difficulty in characterization and (2) analytical techniques will likely evolve over time. In addition, it would not be surprising for FDA to adopt principles from recent EMA draft guidelines. Finally, given the lack of attention paid to interchangeability in the NEJM article, it seems doubtful that FDA will focus much on such requirements in the upcoming guidance.

FDA and industry have also recently reached a "tentative" agreement on the user fee structure for biosimilar applications. Indeed, the proposed user fee structure reflects FDA's expectation that developing a biosimilar product will require more early-stage interaction with FDA. The tentative agreement appears to be similar to the original FDA proposal, which included product development and application fees for pending products as well as product and establishment fees for marketed products. Also, the tentative agreement requires at least $20 million in "non-user fee funds" (read federal funding).

by Kyle Deighan

On September 19, FDA issued a Compliance Policy Guide ("CPG") intending to crack down on countless drug products being marketed in the United States without FDA approval. The CPG."Marketed Unapproved Drugs-Compliance Policy Guide, Sec. 440.100 Marketed New Drugs Without Approved NDAs or ANDAs", makes clear that unapproved drugs introduced on the market after September 19, 2011 are "subject to immediate enforcement action at any time, without prior notice and without regard to the enforcement priorities." This comes as part of FDA's enforcement efforts under the Unapproved Drugs Initiative.

Unapproved Drugs-Compliance Policy Guide, Sec. 440.100 Marketed New Drugs Without Approved NDAs or ANDAs

FDA estimates that as many as several thousand drug products lack approval and are thus being marketed illegally. These products are on the market for various reasons, but in all cases manufacturers have failed to provide FDA with required safety and efficacy data. For these unapproved drugs, FDA stated that it will take steps to encourage the submission of required information from the manufacturers or remove the products from the market.

by Brian Malkin

On September 27, FDA published in the Federal Register a Notice about the availability of a revised guidance, User Fee Waivers, Reductions, and Refunds for Drugs and Biological Products. The Guidance updates an interim guidance issued in July 16, 1993. The Notice explains that the revised guidance was proposed on March 14, 2011 but received no comments by the end of its comment period on June 13, 2011.

The Guidance describes: (1) the types of waivers, refunds, and reductions available under the user fee provisions of the Federal Food, Drug, and Cosmetic Act ("FD&C Act") and (2) procedures for requesting waivers, refunds, or reductions and reconsiderations and appeals of FDA decisions of such requests. FDA's revised guidance also clarifies related issues such as user fee exemptions for orphan drugs.

by Erin Lawrence

On September 19, 2011, Plaintiffs James Sherley and Theresa Deisher, filed a notice of appeal in their lawsuit Sherley v. Sebelius. The appeal asks that the Court of Appeals for the District of Columbia reverse the District Judge Royce Lamberth's July 27th decision that the government can continue to finance embryonic stem cell research. (See our previous blog here).

Judge Lamberth dismissed the Plaintiffs' lawsuit in July citing the Court of Appeals April holding that government-backed research on embryonic stem cells is likely lawful under the Dickey-Wicker Amendment. The appeal now seeks an opposite decision from the same Court of Appeals. The appeal requests that the Court of Appeals block the U.S. Health and Human Services Department and the National Institute of Health from spending federal funds on research involving human embryonic stem cells.

The scientist hired a Christian law firm, Jubilee Campaign to file the appeal. The Jubilee Campaign is spondering the "Law of Life Project" which is dedicated to "defending the right to life and dignity of the human being from biological conception. . . ."

The next step will be for Court of Appeals to set a schedule for submission of legal briefs and oral arguments. Although Plaintiffs' success in the appeal may be a far shot--especially given that the Court of Appeals has already decided that it is highly likely that government funding of embryonic stem cell research is legal--a victory for Plaintiffs' would put the stem cell battle on a path to the U.S. Supreme Court.

by Fitz Beckwith Collings

The U.S. District Court for the middle district of Florida dealt FDA a setback in U.S. v. Franck's Lab, ruling that the agency did not possess the statutory authority to regulate the traditional compounding practices of veterinary pharmacies.

Franck's Lab is a large, Florida-based compounding pharmacy. In 2009, Franck's was responsible for the deaths of 21 Venezuelan national polo team ponies. The deaths were traced to a mathematical error made by one of Franck's prescribing veterinarians during the compounding process. The resulting solution of Biodyl proved too potent, and the Florida Board of Pharmacy imposed fines and reprimanded Franck's. After this incident, FDA expressed concern that Franck's compounded a number of the drugs at its facility outside the context of a valid veterinarian-client-patient relationship. The scope and scale of Franck's production, combined with the alleged lack of a veterinarian relationship, led FDA to conclude that Franck's was operating as a drug manufacturer.

Under Florida state law, pharmacists are permitted to compound a medication when a veterinarian prescribes it for an individual patient. This process enables the veterinarian to tailor the medication to the animal's needs, e.g., by accounting for allergies to ingredients in commercially-available medications. Franck's routinely prepared quantities of compounded medications from bulk substances in the absence of a prior prescription by a veterinarian, with the expressed purpose of maintaining a sufficient supply for new customers. FDA ultimately sought to enjoin Franck's from compounding any quantity of veterinary pharmaceuticals from bulk substances indefinitely - a first for the agency - unless Franck's obtained FDA approval as a drug manufacturer. The central issue in the case was whether the Food, Drug and Cosmetic Act (as originally enacted in 1938) conferred to FDA the authority to enjoin Franck's from engaging in traditional veterinary compounding.

by Howard E. Rosenberg, Ph.D.

On September 14, the Senate Health, Education, Labor and Pensions ("HELP") Committee, chaired by Senator Tom Harkin (D-IA), held a hearing to discuss the issues raised by the recent the Government Accountability Office ("GAO") report, which stated that up to 80% of the chemicals and ingredients of prescription drugs are made outside the United States and that globalization has placed increasing demands on FDA in ensuring the safety and effectiveness of drugs marketed in the United States. While inspections of foreign drug manufacturers are an important element of FDA's oversight of the supply chain, it has been shown in previous GAO reports that FDA conducts relatively few such inspections. Given the difficulties that FDA has faced in inspecting and obtaining information on foreign drug manufacturers, and recognizing that more inspections alone are not sufficient to meet the challenges posed by globalization, the report recognized that the agency had begun to implement other initiatives to improve its oversight of the drug supply chain.

This aspect was addressed by Deborah Autor, Deputy Commissioner for Global Regulatory Operations and Policy, . The Deputy Commissioner described several potential problem areas such as: 1) the increasingly complex path that medical products travel, from raw source materials to finished products for consumers, where at every stage in this process opportunities arise for the product to be contaminated, diverted, counterfeited, or otherwise adulterated and 2) Cargo thefts of prescription drugs, where in 2009 alone, an estimated 46 drug cargo thefts occurred, valued at a total of $184 million. Some of these drugs ended up being used by consumers after being stored at incorrect temperatures and consequently having lost potency.