The U.S. Food and Drug Administration is tightening the potency specifications for levothyroxine sodium, used to treat underactive thyroid glands and other thyroid conditions, to ensure the drug retains its potency over its entire shelf life. This action is being taken in response to concerns that the potency of the drug may deteriorate prior to its expiration date. The change will help improve the quality of the product so that consumers receive the level of medication needed to treat their thyroid disorders. Levothyroxine sodium products are used by over 13 million patients.

FDA is mandating that levothyroxine sodium drug products tighten their potency specifications to meet a 95 percent to 105 percent potency specification until their expiration date. The shelf life is the length of time a drug can be stored before it degrades to unacceptable levels. The 95 percent lower potency specification will ensure the drugs do not degrade by more than 5 percent of the labeled claim before their expiration date and the 105 percent upper specification is appropriate to address occasional analytical testing variability. Currently, these products are allowed a potency range of 90 to 110 percent.

The action is consistent with the recommendations of a joint FDA advisory committee and follows concerns expressed about levothyroxine sodium products by health care professionals and patients. Manufacturers and marketers have two years to comply with the revised specification.

A healthy, functioning thyroid gland is critical to regulating a person's overall metabolic function, which consequently impacts a host of other bodily functions. "These medicines are vital to people taking thyroid replacement or suppression therapies," said Janet Woodcock, M.D., deputy commissioner and chief medical officer and acting director of FDA's Center for Drug Evaluation and Research. "Tightening the potency specifications will ensure that the most vulnerable patients taking thyroid medication will receive the appropriate level of drug therapy needed for their condition."  

Consumers can also help maintain the potency of their medications by storing medications in a dry place at room temperature and avoiding humid, hot environments such as bathrooms, which speed deterioration.

Over the past decade, the FDA has spent considerable resources to ensure that levothyroxine sodium products are safe and effective. The FDA requested and received stability data from manufacturers of all the approved, marketed levothyroxine sodium drug products manufactured between July 2003 and June 2005, and examined the stability profile of each drug.

The data revealed a trend toward a loss of potency, with some preparations showing potency approaching 90 percent of labeled potency by the expiration date. Although all approved levothyroxine sodium products fall within the current potency specification of 90 percent to 110 percent, the stability data showed that some products rapidly degrade over their labeled shelf life. Some strengths or package types, such as blister packs, degrade more rapidly than others, resulting in varying expiration dates within product lines.  In addition, there is variability in expiration dating periods between products from different manufacturers. Some levothyroxine sodium tablets remain very stable, losing less than 5 percent of labeled potency within 24 months, while other products lost approximately 10 percent of labeled potency in 9 months. By tightening the potency specification and limiting the amount that products can degrade throughout their shelf life, FDA is reducing the variability in the stability profiles between products that could have clinical consequences in achieving target thyroid levels, especially for the most vulnerable patients, such as those with thyroid cancer.  

Levothyroxine sodium products have been marketed for decades in the United States.  This class of drugs is used to treat hypothyroidism, as a thyroid replacement therapy, to suppress the growth of benign goiters and thyroid cancer, and as an adjunct to surgery and radioiodine therapy designed to manage some types of thyroid tumors.

For more information:
http://www.fda.gov/cder/drug/infopage/levothyroxine/default.htm

Effort Part of Agency’s Response to Institute of Medicine Recommendations
The U.S. Food and Drug Administration today announced the award of a two-year, $1.5 million contract to the Center for Professional Development (CPD) to assist with the transformation of FDA's Center for Drug Evaluation and Research (CDER), with a particular focus on steps to improve workplace leadership, empower staff, and establish more effective business practices.

The award to Oakland, Calif.-based CPD is part of the FDA’s ongoing response to a report issued in 2006 by the Institute of Medicine (IOM). Under the contract, CPD will help in the development of practical strategies, including training, tools, and processes that will strengthen CDER’s organizational effectiveness and reaffirm its mission of advancing and protecting the public health.

“This transformative program will provide CDER with the tools and expertise necessary to create a sustainable environment of open and transparent communication, collaborative decision-making, and improved morale and staff retention,” said Janet Woodcock, M.D., FDA’s deputy commissioner for scientific and medical programs, chief medical officer and acting center director.

The IOM report, The Future of Drug Safety — Promoting and Protecting the Health of the Public, identified workplace culture issues in CDER and recommended participation of external management consultants to develop a comprehensive strategy to address them. Over the past year, CDER carefully evaluated options and developed a scope of work to solicit the best outside experts to assist in transforming the workplace environment. The entire workforce of about 2,300 in CDER will be included in the workplace transformation effort. CPD will work with CDER’s senior management team and a cross-sectional working group of CDER employees to assess the center’s organizational culture, identify characteristics and a vision for CDER’s desired culture, and develop a plan for implementation and follow-up.

The CPD contract runs through Sept. 20, 2009.

For more information

The Future of Drug Safety — Promoting and Protecting the Health of the Public
FDA's Response to the Institute of Medicine's 2006 Report http://www.fda.gov/oc/reports/iom013007.html#intro

Foundation part of new FDA law
The U.S. Food and Drug Administration is seeking nominations from patient and consumer advocacy groups, professional scientific and medical societies, and industry trade organizations to serve on the board of directors of the newly created Reagan-Udall Foundation.

Title VI of the recently enacted Food and Drug Administration Amendments Act of 2007 created the foundation to advance the mission of FDA to modernize medical, veterinary, food, food ingredient, and cosmetic product development, accelerate innovation, and enhance product safety.

The foundation will be a private, independent, nonprofit entity. The statute calls for a diverse 14-member board: four representatives from the general pharmaceutical, device, food, cosmetic and biotechnology industries; three representatives from academic research organizations; two representatives from patient or consumer advocacy groups; one member representing health care providers; and, four at-large representatives with expertise or experience relevant to the purpose of the Reagan-Udall Foundation.

"A concerted effort by government, industry and academia is needed to modernize the scientific tools used to develop products and to monitor their safety once they go to market," said Commissioner of Food and Drugs Andrew C. von Eschenbach. "We are looking forward to foundation candidates who will work with us to embrace the transformational nature of future efforts to protect and promote the public health."

The foundation will identify unmet scientific needs in the development, manufacture, and evaluation of the safety and effectiveness of FDA regulated products, including post-market evaluation, and establish scientific projects and programs to address those needs. It will help accomplish the scientific work the FDA needs to support its regulatory mission. The foundation will be an important vehicle for private and public stakeholders to collaborate to address the priorities and opportunities identified in FDA's Critical Path reports, and to help modernize the product evaluation sciences.

FDA, the National Institutes of Health, Centers for Disease Control and Prevention, and the Agency for Healthcare Research and Quality have 30 days to appoint the foundation's board of directors. FDA will handle the submission process. Nine members are to be appointed from a list of candidates provided by the National Academy of Sciences. Five members are to be appointed from lists of candidates submitted by organizations mentioned above.

Interested persons may submit nominations by facsimile to Lisa Rovin or Nancy Stanisic at 301-443-9718, or by e-mail to Reagan-Udall-Board@fda.hhs.gov. All nominations must be received on or before Oct. 15, 2007.

For more information, see the Federal Register Notice:
http://www.fda.gov/OHRMS/DOCKETS/98fr/07-4882.htm

Effort will streamline generic drug approval process; provide more options for consumers, health professionals
The U.S. Food and Drug Administration today outlined a program aimed at increasing the number and variety of generic drug products available to consumers and health care providers. Generic drugs generally cost less than their brand-name counterparts and competition among generics has been a key factor in lowering drug prices. The Generic Initiative for Value and Efficiency, or GIVE, will help the FDA modernize and streamline its generic drug approval process.

The agency approved or tentatively approved a record of 682 generic drugs products in fiscal year 2007, over 30 percent more than the previous year.

“To keep pace with the increasing number of generic drug applications, FDA will implement some changes to the generic drug approval process,” said Gary Buehler, director of FDA’s Office of Generic Drugs. “The GIVE plan outlines ways to maximize the use of our resources so that FDA can review and approve even more high quality generic drugs during the upcoming fiscal year than it did in 2007.”

As part of the GIVE efforts, FDA is revising the review order for certain drug applications. For example, first generic products, for which there are no blocking patents or exclusivity protections on the reference listed drug, are identified at the time of submission for expedited review. This will mean that these products, for which there are currently no generic products on the market, may reach the consumer much faster.

FDA now has about 215 full-time staff working on the review of generic drug applications. Under GIVE, FDA will hire and train new generic drug reviewers and focus on enhanced use of electronic programs for handling drug submissions and internal documents. When possible, resources from other FDA departments will be engaged in the effort. As well, FDA will increase its communications with generic drug manufacturers and provide training on proper application submission to the industry in meetings and Webcasts.

Generic drugs undergo a rigorous scientific review to ensure that they are of high quality, safe, and effective. Generic drug manufacturers must demonstrate that a generic drug has the same dosage form, strength, route of administration, and conditions of use as the approved brand-name product. Generic drug manufacturers also must demonstrate bioequivalence, meaning they show that the drug delivers the same amount of its active ingredient in the same amount of time as the brand-name counterpart. Bioequivalence is a critical requirement for concluding that the original and generic drugs will produce the same therapeutic results.

For more information

Generic Initiative for Value and Efficiency (GIVE) www.fda.gov/oc/initiatives/advance/generics.html

New Initiative to Improve Availability of Generics
http://www.fda.gov/consumer/updates/generics100407.html

Consumer Q and A: FDA's New Generic Drug Program
www.fda.gov/consumer/updates/genericsqa100407.html

FDA's Office of Generic Drugs
www.fda.gov/cder/ogd/

The U.S. Food and Drug Administration today approved the first generic versions of Trileptal (oxcarbazepine), an anticonvulsant drug. Generic oxcarbazepine is FDA-approved for use alone or in combination with other medications in the treatment of partial seizures in adults and children aged four years and above.

"FDA requires generic drugs to have the same quality, strength, purity and stability as brand-name drugs," said Gary J. Buehler, director of FDA's Office of Generic Drugs. "The agency ensures that generic drugs are safe and effective, offering alternatives to Americans in choosing their prescription drugs."

Oxcarbazepine tablets in three strengths (150 milligrams, 300 milligrams and 600 milligrams) are manufactured by Roxane Laboratories Inc., Glenmark Pharmaceuticals Limited, and Sun Pharmaceutical Industries Limited.

The labeling of the generic products may differ from that of Trileptal because parts of the Trileptal labeling are protected by patents and/or exclusivity.

According to the publication Drug Topics, Trileptal was 74th best selling brand-name drug in by retail dollars in the United States in 2006.

Serious skin reactions have been reported in children and adults in association with Trileptal use. In the event a skin reaction should occur while taking Trileptal patients should immediately consult with their health care provider. Common side effects reported with Trileptal use include dizziness and drowsiness.

For information:

FDA Generic Initiative for Value and Efficiency
www.fda.gov/oc/initiatives/advance/generics.html

FDA's Office of Generic Drugs
www.fda.gov/cder/ogd/

Frequently asked questions about generic drugs
www.fda.gov/cder/consumerinfo/generics_q&a.htm

Discusses how they can work together to beat disease, ensure safe food, effective drugs
Food and Drug Administration Commissioner Andrew C. von Eschenbach, M.D., met this week with leading officials in China, as part of a series of negotiations launched by Health and Human Services Secretary Mike Leavitt with Chinese counterparts on the safety of food, feed, drugs and medical devices.

The latest meeting provided another opportunity for high-ranking experts from both governments to exchange views and information about their respective efforts to protect and promote the health of their citizens.

Dr. von Eschenbach met with Dr. Zhu Chen, minister of health of the People’s Republic of China, Commissioner of China’s State Food and Drug Administration, Shao Mingli, and Vice Minister Chuanzhong Wei of the Chinese General Administration of Quality, Supervision, Inspection and Quarantine.

“Our discussions were very productive,” said Dr. von Eschenbach. “Minister Chen, Commissioner Shao and Vice Minister Wei are distinguished leaders, who are, like me, dedicated to enhancing the health of the men, women, and children we each serve, and to protecting the safety of our food supply and chain of medical and pharmaceutical products. We are all deeply committed to enhancing the health of the publics we serve.”

During the meeting, both sides framed their discussion in the context of global medical research and public health concerns, all of which the activities of their respective organizations affect.

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Products alleged to violate new drug and misbranding provisions of Federal Food, Drug and Cosmetic Act
At the request of the U.S. Food and Drug Administration (FDA), U.S. Marshals seized on Tuesday approximately $71,000 of goods from FulLife Natural Options, Inc., of Boca Raton, Fla., which marketed and distributed Charantea Ampalaya Capsules and Charantea Ampalaya Tea.

Although these products are labeled as dietary supplements, they are being promoted by FulLife for use in treating serious conditions, such as diabetes, anemia, and hypertension. These claims are evident in the products' labeling, including promotional literature and FulLife's Internet Web site.

The agency takes seriously its responsibility to protect Americans from unapproved drugs. FDA considers these products to be unapproved new drugs because they make claims related to the prevention or treatment of diseases in the products' labeling. Before a new drug product may be legally marketed, it must be shown to be safe and effective, and approved by FDA. Tuesday's action protects consumers who may rely on unapproved products and unsubstantiated claims associated with these products when making important decisions about their health.

The Complaint, filed by the U.S. Attorney's Office for the Southern District of Florida, charges the products are in violation of the drug and misbranding provisions of the Federal Food, Drug and Cosmetic Act.

Following an investigation of the firm's marketing practices, FDA officials advised FulLife that the claims related to prevention or treatment of diseases made these products subject to regulation as drugs. Despite FDA's warnings, the firm failed to bring its marketing into compliance with the law. During subsequent inspections, FDA inspectors found that the offending claims were still being made.

The seizure Tuesday at FulLife is the second such enforcement action in two months taken by FDA against dietary supplements being promoted with drug claims to cure or treat diabetes and other diseases or conditions.

On August 23, 2007, at the request of FDA, U.S. Marshals in the Northern District of Florida seized an estimated $41,000 worth of inventory of Glucobetic, Neuro-betic, Ocu-Comp, Atri-Oxi, Super-Flex, MSM-1000, and Atri-E-400 capsules being promoted and distributed by Charron Nutrition of Tallahassee, Fla., for use in treating diabetes, arthritis, and other serious health conditions.

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Statement by Daniel Schultz, M.D., director of the Center for Devices and Radiological Health:

Medtronic's decision to voluntarily remove its Sprint Fidelis defibrillation leads from the market is in the best interest of patient safety.

These electronic wires are prone to fracture in a small number of patients which can cause the defibrillator to deliver unnecessary shocks or not operate at all. Based on our initial review of reported adverse events, some deaths and major complications have occurred after the leads have fractured.

Defibrillators are life-saving products for patients with a heart rhythm abnormality. We know it can be frightening for a patient to learn that a product they rely on so much might have a serious defect. However, patients can be assured that the likelihood of fracture is very low and FDA is committed to ensuring that the risk to patients is minimized.

Background:
Today, Medtronic announced it was voluntarily suspending distribution of its Sprint Fidelis defibrillation leads because a small number of fractures have been detected. As a result of Medtronic's action, no more Sprint Fidelis leads will be sold or manufactured and any remaining product should be pulled from inventory and returned to the company. Patients who are implanted with this lead are encouraged to contact their physicians for further information.

Medtronic first notified physicians in March about the fracture rate at that time and the proper method for implantation. Additional data on adverse events accumulated since then has prompted today's action.

Implantable cardioverter defibrillators (ICDs) and Cardiac Resynchronization Therapy-Defibrillators (CRT-Ds) are used to treat abnormal heart rhythms that can cause the heart to stop suddenly. ICDs and CRT-Ds shock the heart back into normal rhythm by sending a pulse of energy through an electronic wire or lead that is connected to the heart.

When a defibrillator lead is slightly more prone to fracture, it doesn't mean that every lead will break. Most leads will function well, as is the case with Sprint Fidelis. In the infrequent circumstance where a lead actually breaks, or "fractures," the lead may send false signals that cause inappropriate defibrillator shocks, or therapies such as pacing or shocks may not be delivered.

Current adverse event information indicates that fractures have occurred in less than 1 percent of the approximately 268,000 of these leads implanted worldwide. We don't know if this rate of adverse events will remain constant or increase over the life of these leads.

FDA considers Medtronic's action to be a product recall, as defined by FDA regulations, and we will soon be issuing a recall classification for this action. We recognize that some patients and health care professionals might inappropriately interpret the word "recall" to mean that the devices must be surgically removed and returned to the manufacturer. Although the leads should no longer be implanted in patients, we do not mean to imply that these leads should be surgically removed.

The leads continue to function properly in the vast proportion of patients. Although there is no test to predict which lead will fracture, FDA agrees with Medtronic's recommendation that defibrillator settings be adjusted at the patient's next scheduled follow-up visit with their doctor. Doing so may increase the likelihood that a fracture will be detected before a patient is harmed.

Neither FDA, Medtronic, nor representatives of the Heart Rhythm Society, recommend the routine surgical removal of a fractured lead because removal carries risks. Instead, physicians should weigh the benefits and risks of either continuing to use the lead with careful monitoring or capping the lead so it is no longer useable and implanting a different model.

Patients should recognize that a small number of Sprint Fidelis leads are used with defibrillators made by manufacturers other than Medtronic. If patients have reason to believe that they have a Sprint Fidelis lead or if they do not know the model of their lead, they should contact their health care professional.

FDA will continue to monitor information on these devices and will take whatever other actions may be necessary.

Gerald F. Masoudi has been appointed as associate general counsel/chief counsel of the Food and Drug Division of the United States Department of Health and Human Services' Office of the General Counsel, which handles legal matters for the U.S. Food and Drug Administration.

Since 2005, Masoudi has been deputy assistant attorney general in charge of International, Policy and Appellate Matters in the Antitrust Division at the U.S. Department of Justice.served as principal deputy associate general counsel for the Food and Drug Division, serving for a time as acting associate general counsel. Before joining the Food and Drug Division, Masoudi was a partner at Kirkland & Ellis LLP.

"We are pleased to have Jerry's expertise and insight back at HHS," said Commissioner of Food and Drugs Andrew C. von Eschenbach, M.D. "His leadership and service will be critical to FDA's public health mission and regulatory responsibilities."

Masoudi earned his bachelor's degree from Amherst College in 1990. He graduated with high honors from the University of Chicago Law School in 1993, where he was an editor of the Law Review. He also clerked for Judge Frank H. Easterbrook of the U.S. Court of Appeals for the Seventh Circuit.

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Raltegravir Tablets Used in Combination with Other Antiretroviral Agents

The U.S. Food and Drug Administration (FDA) has approved raltegravir tablets for treatment of Human Immunodeficiency Virus (HIV)-1 infection in combination with other antiretroviral agents in treatment-experienced adult patients who have evidence of viral replication and HIV-1 strains resistant to multiple antiretroviral agents.

Raltegravir is the first agent of the pharmacological class known as HIV integrase strand transfer inhibitors, designed to interfere with the enzyme that HIV-1 needs to multiply. Raltegravir, sold under the trade name Isentress, received a priority review by the FDA.

“This is an important new product for many HIV-infected patients whose infections are not being controlled by currently available medications,” said Janet Woodcock, M.D., FDA’s deputy commissioner for scientific and medical programs, chief medical officer and acting director, Center for Drug Evaluation and Research.

When used with other anti-HIV medicines, raltegravir may reduce the amount of HIV in the blood and may increase white blood cells, called CD4+ (T) cells, that help fight off other infections.

FDA’s approval of raltegravir is based on data from two double-blind, placebo-controlled studies in 699 HIV-1 infected adult patients with histories of extensive antiretroviral use. A greater proportion of the patients who received raltegravir in combination with other anti-HIV drugs experienced reductions in the amount of HIV in the blood, compared with patients who received placebo in combination with other anti-HIV drugs.

The most common adverse events reported with raltegravir were diarrhea, nausea, and headache. Blood tests also showed abnormal elevated levels of a muscle enzyme in some patients receiving raltegravir. Caution is advised when using raltegravir in patients at increased risk for certain types of muscle problems, including those who use other medications that can cause muscle problems.

Patients taking raltegravir may still develop infections, including opportunistic infections or other conditions that may develop in patients living with HIV-1 infection. The long-term effects of raltegravir are not known, and its safety and effectiveness in children less than 16 years of age has not been studied.

Raltegravir also has not been studied in pregnant women. Women who are taking HIV medications when they get pregnant are advised to talk with their physician or other health care professional about use of this drug during pregnancy, and about registering with the Antiviral Pregnancy Registry if they use raltegravir.

Raltegravir is distributed by New Jersey-based Merck & Co., Inc.