FDA Lawyers Blog

by Brian Malkin

FDA Lawyers Blog is pleased to announce that its style sheets for iPhones and Android smartphones are now complete. These style sheets are In addition to mobile apps for iPhones and Android smartphones that can be downloaded directly from the Apple App Store and the Android Market free of charge. Together, FDA Lawyers Blog's mobile style sheet and iPhone and Android apps provide a new global level of accessibility and usefulness for professionals in the field of FDA law.

As we previously mentioned, the mobile style sheets make FDA Lawyers Blog more readable on your iPhone or Android smartphone. First, the style sheets provide you with an initial pop-up to choose to download the iPhone app, the Android app, or to go directly to the mobile style sheets for the blog ("TAP HERE TO CLOSE"). You should only see this pop-up once unless you clear your browser's cache (cookies and data).

Once you enter FDA Lawyers Blog's mobile style sheets, you are provided with a similar but somewhat different interface than the full version of FDA Lawyers Blog. Recognizing that individuals utilizing FDA Lawyers Blog on the move may want to locate particular blog items quickly, we moved a search bar up to the top (as opposed to a separate "Search" tab in the full blog). The most recent blog appears as it does on the full version of the blog, whereas older blog items are truncated after about a paragraph to make scrolling to blog items easier with "Continue reading" features to permit readers to view the full blog. To make reading the blog items easier, the mobile version focuses on the text in the blog, increasing its font size to permit readability in an upright mode without the need to flip the phone on its side or increase font size on the screen.

Following the most recent blogs are other features found on the full version of the blog. First, there is the contact screen, then subject headings to locate particular blogs by subject, then the "Events" and "Articles" tabs that feature FDA Lawyers Blog contributors on FDA-related topics.

Towards the bottom of the screen is a button "View Full Version" that permits readers to toggle to the full version of FDA Lawyers Blog on an iPhone or Android smartphone. When you want to go back to the mobile version, towards the bottom right-hand corner of the full version is a button "View Mobile Version" that permits readers to toggle to the mobile style sheets once again.

We hope that you enjoy both the mobile style sheets and iPhone or Android smartphone apps. Please continue to watch for additional updates as we listen to your comments about what you need to be more productive with regard to FDA news and updates.

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by Julie E. Kurzrok

Several of the top-selling drugs in the U.S. will be losing their patent protection within the next 14 months, resulting in a potential savings of 40-80% for consumers. This will be the largest group of pharmaceuticals to go generic. Most notably, as of November 30, 2011, generic versions of the cholesterol-lowering medication Lipitor® will be available. Lipitor® (atorvastatin calcium) is the highest-selling drug in the U.S., with 2010 U.S. revenues of $5.3 billion. On November 30, 2011, it is anticipated Watson will release its authorized generic version of Lipitor®, and with FDA approval, Ranbaxy would be able to release its generic Lipitor®. There are at least nine other generic companies that could potentially launch generic Lipitor® on May 28, 2012, after the expiration of Ranbaxy's 180-day exclusivity as the first applicant with a patent challenge. For this product alone, the potential generic competition could cut consumers' spending by $6 billion by the year 2015.

Plavix® (clopidogrel bisulfate), the most prescribed drug to prevent heart attack and stroke, is another top-seller that will lose U.S. exclusivity in May 2012. Additional examples of drugs set to lose patent protection in 2012 include the antipsychotic Seroquel® (quetiapine fumarate) and the asthma drug Singulair® (montelukast sodium). While the patent on the type II diabetes drug Actos® (pioglitazone hydrochloride) has already expired, Takeda, the drug's manufacturer, has an agreement with several generic companies that they will not market generic versions until August 2012. While the damages to innovator drug manufacturers may be substantial (e.g., between 2010-2012 Pfizer will lose patent protection for drugs currently accounting for about 42% of its revenue), the influx of generic drugs into the market is positive news for both consumers and generic drug companies.

For example, the generic company Mylan, which in 2012 plans to introduce generic versions for Plavix®, Actos®, and for Lipitor® in Europe, along with 500 other products, stands to increase its sales by $800 million. The savings for consumers will be substantial considering the average retail drug costs of some of these brand-name blockbusters (Plavix® at approximately $750 per month, Actos® at approximately $250 per month, Lipitor® at approximately $150 per month). As more generic versions of these popular innovator products become available to consumers, consumers and their insurance providers win by reduced costs.

by Brian Malkin

On November 1, the Centers for Disease Control and Prevention ("CDC") published in its publication, Morbidity and Mortality Weekly Report ("MMWR"), the results of a study that confirmed the epidemic of overdoses of opioid pain relievers ("OPRs") has continued to worsen particularly from 1999-2008. OPR deaths now account for more drug overdose deaths than heroin or cocaine combined and represent nearly 75% of all prescription drug overdose deaths. Drug overdose deaths (36,450) are now almost as high as the number of deaths from motor vehicles (39,973), which is the leading cause of injury death in the United States.

What is also alarming is that the OPR overdose rates have continued to rise despite increased warnings and recommendations over the past decade for voluntary education of health-care providers about more cautious use of OPRs. According to the MMWR, the death rate of drug overdoses of 11.8 per 100,000 population (nearly 100 people per day) is about three times the rate in 1991. Since 1999, most of the drug overdose increases have been attributed to prescription drug overdoses. In 2009 alone there were 1.2 million emergency department visits related to misuse of pharmaceuticals, which represented a 98.4% increase from 2004, compared to 1.0 million for use of the illegal drugs heroin and cocaine.

According to the MMWR, sales of OPRs quadrupled between 1999 and 2010 so that by 2010 enough OPRs were sold to mediate every American adult with a typical dose of hydrocodone every 4 hours for 1 month. Increased use of OPRs has contributed to overall increases in overdose death and nonmedical use. Yet the total number of prescribers responsible for the increase appears to be small: one study found only 3% of physicians accounted for 62% of the OPRs prescribed. Once prescribed, OPRs may be diverted for nonmedical uses (i.e., to patients for whom the drug was not prescribed or for other uses not attributed to pain for whom the drug was prescribed) or sold on the street. In 2010, 4.8% of the U.S. population 12 and older reportedly used OPRs nonmedically. This, in turn, cost insurance companies up to $72.5 billion in health-care costs.

by Brian Malkin

On October 31, a preliminary report of a new California study was presented at the American Public Health Association in Washington, D.C. that appears to demonstrate that state vaccination "personal belief exemptions" are resulting in "hot spot" zones where children are at greater risk of exposure to preventable infectious diseases such as measles, mumps, and rubella.

The new California study analyzed state health department statistics for personal belief exemptions among kindergartners. Personal belief exemptions are affidavits signed by parents indicating that "all or some immunizations are contrary to my beliefs," which permits children to avoid otherwise mandated vaccines. Twenty states allow personal belief exemptions including California.

According to the study, in 2010 for every 100 children in a California kindergarten, 2.3 had skipped immunizations because of one or more personal belief exemptions. Interestingly, the exempted children tended to cluster in certain schools, where an average of 16 out of 100 of their peers also claimed exemptions. Some schools had one in five kindergartners with parental exemptions for vaccinations. More than 7,000 kindergartners across California attended these schools, including 2,700 who were exempted.

by Julie E. Kurzrok

It has long been known that there is an increased risk of cardiovascular complications including, for example, blood clots known as venous thromboembolisms ("VTEs") that result from the use of combined hormonal contraceptives ("CHCs"). Most CHCs are birth control pills containing the hormones estrogen and progestin. Recently, several new CHCs have been introduced into the market, and concerns have arisen regarding whether the cardiovascular risks are greater among these new preparations. The new CHCs are drospirenone/ethinyl estradiol tablets, the norelgestromin/ethinyl estradiol transdermal patch, and the etonogestrel/ethinyl estradiol vaginal ring. Drospirenone is a synthetic progestin, and the drospirenone tablets are marketed under the names Yaz®, Yasmin®, Beyaz®, and Safyral® (along with various generics). On October 27, 2011, the FDA published the final study report from its evaluation of these risks along with a safety statement regarding the possible increased risk of VTEs from drospirenone tablets.

FDA's study was a retrospective study entitled, "Combined Hormonal Contraceptives (CHCs) and the Risk of Cardiovascular Disease Endpoints" and it compared the risk of blood clots, among other things, in women who took three newly-marketed CHCs to women who took four older CHCs. The study examined the medical histories of 835,826 women from 2001 to 2007 and found that women taking the newly-marketed CHCs, including the drospirenone tablets, had a significantly higher risk of VTEs. Among only the users of the new formulations, the drospirenone tablets were the only ones with a significantly higher risk of VTEs. In conclusion, FDA stated that this study provided further evidence to link the drospirenone tablets with an increase in VTEs as compared to the other low-dose CHCs.

However, FDA has also seen conflicting results from six other studies of drospirenone pills and the risk of VTEs. Because of the conflicting results, FDA will hold a joint meeting with scientific advisors from the Reproductive Health Drugs Advisory Committee and the Drug Safety and Risk Management Advisory Committee on December 8, 2011. At the meeting FDA will review the results of its study and discuss the risks and benefits of drospirenone birth control pills, especially the risk of blood clots associated with these pills.

by Kyle Deighan

On October 14, Par Pharmaceutical, Inc. ("Par") filed a complaint against the United States of America and the Food and Drug Adminstration ("FDA") seeking a declaratory judgment that the first amendment bars the FDA from criminalizing pharmaceutical manufacturers for making statements regarding so called "off-label promotion" of approved drugs. Par argues that "the ongoing threat of prosecution for alleged off-label promotion based on Par's truthful and non-misleading speech to healthcare professionals concerning the FDA-approved use of Par's FDA-approved prescription drug currently chills Par's speech. Par seeks declaratory and injunctive relief to ensure its ability to engage in this protected speech free from the risk of criminal liability."

Par seeks this relief to allow it to discuss "off-label" uses for its drugs, which refers to use of the product outside that approved by the FDA. According to the complaint, off-label use is widespread and widely accepted by healthcare professionals, the U.S. government, and even the FDA. Par states that "FDA itself has recognized that 'in certain circumstances, off label uses of approved products are appropriate, rational, and accepted medical practice. FDA knows that there are important off label uses of approved drugs.'" Further, Par explains that the government encourages off-label use as well, as many off-label uses are subsidized by the federal government under the Medicare and Medicaid programs.

by Andrew S. Wasson

One would think that the passage of the Biologics Price Competition and Innovation Act in 2010 ("BPCIA") would have quieted the long debate on the appropriate period of exclusivity to award innovators of biological products. Not so. Even after the passage of the BPCIA, President Obama, for one, has been stubbornly attempting to chip away at the 12-year period of exclusivity guaranteed by the act. For example, the FY2012 Budget Plan called for reducing the period of exclusivity to seven years, citing a proposed $2.3 billion in savings by 2021. Supporters of a seven-year period threatened to revisit the issue in the Trans-Pacific Partnership trade talks which occurred this summer.

More recently, President Obama's "Plan for Economic Growth and Deficit Reduction" released in September 2011 yet again called for a reduction of the period of exclusivity to seven years. The plan also suggested prohibiting, "additional periods of exclusivity for brand biologics due minor changes in product formulations, a practice often referred to as 'evergreening.'" The plan asserts that a seven-year period of exclusivity retains "appropriate incentives" for biological innovators -- a point sharply disputed by said biological innovators. The report projected an increase in savings (up to $3.5 billion) over ten years.

In response, a group of fifty-one members of the House of Representatives, mostly Democrats, wrote President Obama, voicing their opposition to the proposed shorter length of exclusivity. The Representatives noted that twelve-year period is currently the law of the land, and enjoys bicameral, bipartisan support. The letter argues that the twelve-year period already strikes the balance between encouraging innovation and access to patients, especially considered upon the pre-BPCIA backdrop where innovators effectively enjoyed exclusivity in perpetuity. The Representatives warned that a shorter period of exclusivity could result in jobs moving overseas.

by Fitz Beckwith Collings

FDA has given the green light to AquaBounty's genetically-engineered salmon, the "AquAdvantage." The fast-growing fish, an Alaskan salmon supplemented with genes from the ocean pout and the Chinook salmon, can mature in 18 months instead of 36. The company first submitted its food to FDA for review in 1995 and now it appears, after a lengthy period of review and public comment, that it is closer than ever before to supermarket shelves. FDA's approval now sits on the desk of the White House's Office of Management and Budget.

As the world's first genetically-engineered animal food, AquAdvantage salmon would undoubtedly require strict oversight. AquaBounty insists that all its genetically-engineered salmon would be bred in inland farms, far from flood plains. But, in contrast to invasive species like the asian carp and the snakehead that must travel in a mating pair, a single escaped AquAdvantage salmon could breed with native salmon species and contaminate the gene pool. Of greater is concern is the possibility that, with its superior growth abilities and its improved resistance to cold temperatures, an escaped AquAdvantage salmon could eventually supplant Alaskan salmon in the wild.

In light of this threat, several groups have mobilized to oppose the approval, including the U.S. Senate. Senators Mark Begich (D-AK) and Lisa Murkowski (R-AK) have introduced an agricultural appropriations amendment--the Prevention of Escapement of Genetically Altered Salmon in the United States (PEGASUS) Act--that would make it a crime "to have custody, control, or possession of, with the intent to ship, transport, offer for sale, sell, or purchase genetically altered salmon or other marine fish, or a product containing genetically altered salmon or other marine fish, in interstate or foreign commerce." The senators sponsoring the amendment represent the state of Alaska, where salmon fisheries are relatively fertile. A similar bill was introduced in the House in June, and both bills would prevent FDA from using funds to approve genetically-engineered fish. House and Senate bills seeking mandatory labeling of genetically-engineered foods are also pending.

by Brian Malkin

On October 23, the 25th Annual Meeting and Exposition of the American Association of Pharmaceutical Scientists ("AAPS") kicked off with a Keynote Address from FDA' Director for the Center for Drug Evaluation and Research, Janet Woodcock, M.D., reflecting on the past 25 years of drug regulation and how they may help inform the next 25 years. Woodcock's premise was that the macroenvironment is a driver for the changes she has seen and expects to see in the future.

by Brian Malkin

FDA Lawyers Blog wanted to make you aware that there are important updates for their mobile apps for iPhones and Android smartphones. The apps feature FDA Lawyers Blog, key FDA news feeds, and a phone-ready HHS directory and can be downloaded directly from the Apple App Store and the Android Market free of charge. The iPhone update makes the app compatible with iOS5 and the Android app fixes a minor stability issue.

We previously mentioned that FDA Lawyers Blog was in the process of optimizing its blog to make it more readable on your iPhone or Android smartphone. We are almost done with those changes, but we will let you know when it is complete. We hope that you find the blog more readable on your smartphone whether you choose to use the apps or the native browser on your phone. Please note that if you choose not to select downloading one of the apps for your phone, the app pop-up will not appear again unles you clear the cache in your phone's browser.

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.

by Brian Malkin

On October 19, FDA published in the Federal Register proposed amendments to its 1992 Orphan Drug Regulations. According to the notice, the amendments "are intended to clarify regulatory provisions and make minor improvements to address issues that have arisen since those regulations were issued." FDA said it has reviewed over 3,350 orphan-drug designation requests since the 1992 regulation became final. This proposed rule follows FDA's announcement of boosting its orphan drug program, as we reported here. Comments are due by January 17, 2012 on the proposed rule.

The specific issues addressed in the proposed rule include:

(1) Demonstration of an appropriate "orphan subset" of persons with a particular disease or condition that otherwise affects 200,000 or more people in the United States, for the purpose of designating a drug for use in that subset;

(2) Eligibility for orphan-drug designation of a drug that is otherwise the same orphan-drug indication as a previously-approved drug;

(3) Eligibility for multiple orphan-drug exclusive approvals when a designated orphan drug is separately approved for use in different subset of the rare disease or condition;

(4) Requirement for demonstrating clinical superiority for the purpose of orphan-drug exclusive approval;

(5) Requirement for submitting the name of the drug in an orphan-drug designation request;

(6) Required drug description and scientific rationale in a designation request;

(7) Required information in a designation request relating to the sponsor's interest in the drug;

(8) Timing of a request for orphan-drug designation;

(9) Responding to a deficiency letter from FDA on an orphan-drug designation request;

(10) FDA publication of information regarding designated orphan drugs;

(11) FDA recognition of orphan-drug exclusive approval;

(12) Miscellaneous terminology changes; and

(13) An address change.

by Charles J. Raubicheck

The Generic Drug User Fee Agreement ("GDUFA") negotiated between the Agency and industry trade associations calls for abbreviated new drug application ("ANDA") applicants to pay a voluntary one-time fee to reduce the significant backlog of ANDAs under review. The payments would be used to hire more reviewers and speed up approvals.

FDA is weighing the impact of the fee on companies who elect to pay it to release particular products from the backlog for stepped-up approval, versus companies who do not. On October 5, Office of Generic Drugs ("OGD") Acting Director Keith Webber told Generic Pharmaceuticals Association ("GPhA") Technical Conference attendees that a major issue could arise--whether a backlogged drug for which a fee is not paid can be denied approval.

Fairness will play a part, Webber said. Payers may contest drug approvals for non-payers. On the other hand, Webber noted that a public health need for a low-cost generic product, where the applicant is a non-payer, would need to be addressed. (Also, smaller generic companies may lack the resources to pay the fee.)

The FDA-industry agreement still has to be approved by Congress in user fee legislation.

by Kyle Deighan

Counterfeit drugs are widely recognized as a serious and growing public health hazard. Around the world, they have become a multi-billion dollar industry, with some estimating sales as high as $75 billion in 2010 alone. Whether to eliminate the risk to the public or to regain profits lost to counterfeiters, the pharmaceutical drug industry has taken notice of the problem, exploring various methods to thwart production and distribution of the phony drug products.

Last week, FDA stepped in when they released a final Guidance directing manufacturers in the pharmaceutical industry on the implementation of a specific anticounterfeiting method--the use of physical-chemical identifiers in drugs. The guide, titled "Incorporation of Physical-Chemical Identifiers into Solid Oral Dosage Form Drug Products for Anticounterfeiting," defines physical-chemical identifiers ("PCIDs") as a "substance or combination of substances possessing a unique physical or chemical property that unequivocally identifies and authenticates a drug product or dosage form."

Essentially, PCIDs are intended to make drug products more difficult to duplicate. Manufacturers add a small amount of an ingredient, the PCID, to the drug product, and "a unique physical-chemical characteristic of that ingredient makes it possible to detect and authenticate legitimate dosage forms, and to identify counterfeits." The guide states that PCIDs include inks, pigments, flavors, and molecular taggants, which may be detected by a patient simply observing the drug, or by more complex means using detection instruments.

by Brian Malkin

On December I, FDA plans to hold a Joint Meeting of the Drug Safety and Risk Management Advisory Committee and the Dermatologic and Ophthalmic Drugs Advisory Committee to discuss "REMS-related topics" including the Risk Evaluation and Mitigation Strategies ("REMS") program for isotretinoin called iPLEDGE.

iPLEDGE is the latest version of one of the oldest and most restrictive risk management programs that continues to receive criticisms because of its mandatory requirements that are viewed by some as burdensome while others as not restrictive enough. Specifically, iPLEDGE fails to do what it set out to do--prevent isotretinoin-related pregnancies that have a high likelihood to result in birth defects even for small amounts given during the early weeks after conception, when a woman may not know that she is pregnant. Birth defects associated with isotretinoin exposure to fetuses have included: hydrocephaly (enlargement of the fluid-filled spaces in the brain), microcephaly (small head and brain), mental retardation and other learning disabilities, ear and eye abnormalities, cleft palate and other facial abnormalities, and heart defects. If that is not enough, the drug also increases the risk of premature birth and infant death.

FDA Lawyers Blog is proud to announce that for six years years running, FLH Partner Charles J. Raubicheck as been recognized as an FDA "Super Lawyer" in Thompson Reuter's Super Lawyers publication for the New York Metro area. The process to become a "Super Lawyer" begins with peer nominations, then candidate research, and ends with a review of candidates by their peers within their primary area of practice.