The U.S. Food and Drug Administration has licensed a new vaccine to protect against smallpox, a highly contagious disease with the potential to be used as a deadly bioterror weapon.

The vaccine, ACAM2000, is intended for the inoculation of people at high risk of exposure to smallpox and could be used to protect individuals and populations during a bioterrorist attack. It will be included in the Center for Disease Control and Prevention's (CDC) Strategic National Stockpile of medical supplies.

A worldwide vaccination program eradicated smallpox in the population. The last case of naturally occurring smallpox in the U.S. was in 1949 and the last case in the world was reported in Somalia in 1977. Known stockpiles of the virus are kept only in two approved labs in the United States and Russia. The CDC considers it a Category A agent, meaning it presents one of the greatest potential threats for harming public health.

Smallpox is caused by the variola virus, a virus that emerged in human populations thousands of years ago. It spreads through close contact with infected individuals or contaminated objects, such as bedding or clothing. There is no FDA-approved treatment for smallpox and the only prevention is vaccination.

"The licensure of ACAM2000 supplements our current supply of smallpox vaccine, meaning we are more prepared to protect the population should the virus ever be used as a weapon," said Jesse L. Goodman, M.D., M.P.H., director of FDA's Center for Biologics Evaluation and Research. "This vaccine is manufactured using modern cell culture technology allowing rapid and large scale production of a vaccine with consistent product quality."

The symptoms of smallpox typically began with high fever, head and body aches. A rash followed that spread and progressed to raised bumps and pus-filled blisters that crusted, scabbed, and fell off after about three weeks, leaving a pitted scar. The fatality rate historically was about 30 percent, according to the CDC.

ACAM2000 is made using a pox virus called vaccinia, which is related to but different from the virus that causes smallpox. The vaccine contains live vaccinia virus and works by causing a mild infection that stimulates an immune response that effectively protects against smallpox without actually causing the disease.

The vaccine is derived from the only other smallpox vaccine licensed by FDA, Dryvax, approved in 1931 and now in limited supply because it is no longer manufactured.

Although smallpox vaccination ended in the United States in 1972 because it was no longer needed for prevention, the U.S. military resumed vaccination of at-risk personnel in 1999, after concluding that the disease posed a potential bioterrorism threat.

"Smallpox could be a particularly dangerous biological threat to us that would kill or debilitate a high percentage of the population," said Rear Adm. W. Craig Vanderwagen, M.D., assistant secretary for preparedness and response, U.S. Department of Health and Human Services. "The licensing of ACAM2000 will make us better prepared as a nation because it provides an important, effective tool for protecting first responders and individuals with a high risk of exposure from this potentially lethal disease."

ACAM2000 was studied in two populations: those who had never been vaccinated for smallpox and those who had received smallpox vaccination many years earlier. The percentage of unvaccinated persons who developed a successful immunization reaction was similar to that of Dryvax. ACAM2000 also was found to be acceptable as a booster in those previously vaccinated for smallpox.

Because ACAM2000 contains live vaccinia virus, care must be taken to prevent the virus from spreading from the inoculation site to other parts of the body, and to other individuals.

To minimize known risks, the vaccine licensing is subject to a Risk Minimization Action Plan (RiskMAP). The RiskMAP requires providers of the vaccine and patients to be educated about these and other risks. The RiskMAP also requires patient education through an FDA-approved Medication Guide for those who receive the vaccine.

The Medication Guide explains the proper care of the vaccination site and provides information about serious side effects that can occur with ACAM2000. In studies, about 1 in 175 healthy adults who received smallpox vaccine for the first time developed inflammation and swelling of the heart and/or surrounding tissues (myocarditis and/or pericarditis). Of the 10 affected adults, four had no symptoms and at the end of the study, all but one had their symptoms resolve.

ACAM2000 is manufactured by Acambis Inc. of Cambridge, England and Cambridge, Mass. Dryvax was made by Wyeth Laboratories Inc. based in Madison, N.J.

FDA Issues Warning Letter to Melanocorp, Inc. For Illegal Sale of Melanotan II
Agency warns consumers about using and purchasing unapproved product
The U.S. Food and Drug Administration (FDA) has issued a Warning Letter to Brian Manookian, owner of Melanocorp, Inc. in Hendersonville, Tenn. for the illegal sale and marketing of the product Melanotan II, which is not FDA-approved, on Melanocorp's Web site. FDA recommends that consumers who are currently using Melanotan II stop using this product and consult their health care provider if they have experienced any adverse events that they suspect are related to its use.

"This product is being mislabeled, marketed and sold illegally as a preventative against skin cancer and as a tanning agent," said Steven Galson, M.D., M.P.H. director of FDA's Center for Drug Evaluation and Research. "Protecting the public from unapproved products such as this that make unsubstantiated claims and may pose a health risk is a top priority at the FDA."

Melanocorp, Inc. advertises the product Melanotan II on its Web site as an injectable tanning product, with additional claims that it is effective in protecting against skin cancer and rosacea (a flushing and redness of the skin). These claims cause Melanotan II to be classified as a drug under the Federal Food, Drug and Cosmetic Act, as well as a new drug because there is no evidence that it is generally recognized as safe and effective for its labeled uses. This product does not have an approved new drug application, and the product's Web site makes false and misleading statements. The product's introduction and delivery into interstate commerce, therefore, violates federal law. The risks run by patients who use unapproved new drugs could include adverse side effects from inappropriately prescribed medications, dangerous drug interactions, and harm from contaminated, counterfeit or outdated drugs. The FDA cautions consumers about injecting any substance, particularly products that are not FDA-approved, into their bodies without the oversight of a licensed health care provider.

Issuance of this Warning Letter is consistent with FDA's focus on fraudulent products marketed on the Internet for serious and life-threatening diseases. Individuals and firms that do not resolve violations of the Federal Food, Drug, and Cosmetic Act risk injunction to halt the illegal activities, seizure of violative products, and other regulatory sanctions.

Consumers and health care providers should notify FDA of any complaints or problems associated with these products. These reports may be made to MedWatch, FDA's voluntary reporting program, by phone at 1-800-FDA-1088, or online at www.fda.gov/medwatch/report.htm.

FDA's Warning Letter is available on FDA's Web site at http://www.accessdata.fda.gov/scripts/wlcfm/recentfiles.cfm.

The U.S. Food and Drug Administration today approved the first generic versions of Coreg (carvedilol).  Coreg is a widely used medication that is FDA-approved to treat high blood pressure, mild to severe chronic heart failure and left ventricular dysfunction following a heart attack.

"The agency's Office of Generic Drugs ensures that generic drugs are safe and effective through a rigorous scientific and regulatory process," said Gary J. Buehler, director, FDA's Office of Generic Drugs. "Generic drugs, which use the same active ingredients as brand-name drugs and work the same way, offer alternatives to Americans in choosing their prescription drugs."

Carvedilol tablets in four strengths (3.125 milligrams, 6.25 milligrams, 12.5 milligrams and 25 milligrams) are manufactured by multiple generic drug companies. The following company’s applications were approved today: Actavis Elizabeth LLC; Apotex Inc.; Aurobindo Pharma Limited; Caraco Pharmaceutical Laboratories Limited; Dr. Reddy’s Laboratories; Glenmark Pharmaceuticals Limited; Lupin Limited; Mylan Pharmaceuticals Inc.; Ranbaxy Laboratories Ltd.; Sandoz Inc.; Taro Pharmaceutical Industries Ltd.; TEVA Pharmaceuticals USA; Watson Laboratories Inc.; and Zydus Pharmaceuticals USA Inc.

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

According to the publication Drug Topics, Coreg was the 30th top selling brand name drug by retail dollars in 2006.

For information:

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.

FDA Approves New Uses for Evista
Drug Reduces Risk of Invasive Breast Cancer in Postmenopausal Women
The U.S. Food and Drug Administration today approved Evista (raloxifene hydrochloride) for reducing the risk of invasive breast cancer in postmenopausal women with osteoporosis and in postmenopausal women at high risk for invasive breast cancer. Evista is only the second drug approved to reduce the risk of breast cancer.

Evista is commonly referred to as a selective estrogen receptor modulator (SERM). In reducing the risk of invasive breast cancer, SERMs may act by blocking estrogen receptors in the breast.

"Today's action provides an important new option for women at heightened risk of breast cancer," said Steven Galson, M.D., M.P.H., director, FDA's Center for Drug Evaluation and Research. "Because Evista can cause serious side effects, the benefits and risks of taking Evista should be carefully evaluated for each individual woman. Women should talk with their health care provider about whether the drug is right for them."

On July 24, 2007, FDA's Oncology Drugs Advisory Committee recommended approval of Evista for reducing the risk of invasive breast cancer in postmenopausal women with osteoporosis and in women at high risk for breast cancer.

In 1997, FDA approved Evista for the prevention of osteoporosis in postmenopausal women and, in 1999, for the treatment of postmenopausal women with osteoporosis.

Breast cancer is the second leading cause of cancer death in American women and accounts for 26 percent of all cancers among women. An estimated 178,480 new cases of invasive breast cancer are expected to occur among women in the United States during 2007. Invasive breast cancer develops when abnormal cells spread into the surrounding breast tissue.

Three clinical trials in 15,234 postmenopausal women comparing Evista to placebo (no drug) demonstrated that Evista reduces the risk of invasive breast cancer by 44 to 71 percent. A fourth clinical trial in 19,747 postmenopausal women at high risk for developing breast cancer compared Evista to tamoxifen. In this trial, the risk of developing invasive breast cancer was similar for the two treatments. The clinical trials were conducted over the last 10 years.

Evista can cause serious side effects including blood clots in the legs and lungs, and death due to stroke. Women with current or prior blood clots in the legs, lungs, or eyes should not take Evista. Other potential side effects include hot flashes, leg cramps, swelling of the legs and feet, flu-like symptoms, joint pain, and sweating. Evista should not be taken by premenopausal women and women who are or may become pregnant because it may cause harm to the unborn baby. In addition, Evista should not be taken with cholestyramine (a drug used to lower cholesterol levels) or estrogens.

The benefits and risks of taking Evista should be carefully weighed in each individual woman. Evista does not completely prevent breast cancer. Breast examinations and mammograms should be done before starting Evista and regularly thereafter.

The product is manufactured by Eli Lilly and Company, Indianapolis, Ind.

For more information, visit: http://www.hhs.gov/breastcancer/

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FDA Licenses 15 New Blood Typing Tests
Tests help ensure safe blood transfusions for patients
The U.S. Food and Drug Administration today licensed 15 new blood typing tests that were previously unavailable in the United States.

These tests, known as blood grouping reagents, are used to determine the blood type of blood donors, an essential step in ensuring safe blood transfusion for patients. If mismatched blood is administered to a patient, it may cause a serious and potentially fatal reaction. To prevent such problems, people must receive compatible blood based on the results of blood typing tests.

The newly approved ALBAclone Blood Grouping Reagents include the common ABO and Rh tests, plus tests for rare blood types. The reagents are monoclonal antibodies, highly specific antibodies that ensure product uniformity and availability.

"The licensing of these reagents will provide more choice for blood establishments and transfusion services and may facilitate testing for rare blood groups," said Jesse L. Goodman, M.D., M.P.H., director of FDA's Center for Biologics Evaluation and Research. "Licensure of these additional blood grouping reagents will help ensure a more stable supply of these tests, especially important in the event of a product shortage."

The reagents are manufactured by Alba Bioscience, Inc. of Durham, N.C.

Two U.S. Department of Health and Human Services agencies will collaborate in the most comprehensive study to date of prescription medications used to treat attention deficit hyperactivity disorder (ADHD) and the potential for increased risk of heart attack, stroke or other cardiovascular problems.

Researchers supported by the Agency for Healthcare Research and Quality and the U.S. Food and Drug Administration will examine the clinical data of about 500,000 children and adults who have taken medications used to treat ADHD, to determine whether those drugs increase cardiovascular risks.

Because medications used to treat ADHD can increase heart rate and blood pressure, there are concerns about the drugs' potential to increase cardiac risks. It is also thought these risks may be different for adults and children, but more evidence is needed about the long-term effects of using ADHD medications.

The planned analysis follows an FDA-sponsored preliminary study that compiled information from large health care databases on prescription drug use, inpatient care, outpatient treatment, and health outcomes, including death. Based on that effort, researchers identified people who took ADHD drugs during a seven-year period ending in 2005. AHRQ, which sponsors research on clinical effectiveness and safety, will team with FDA to complete the analysis of the data.

"This study highlights one of AHRQ's most important missions:  to collect and analyze, scientific evidence that will help patients, policymakers, and clinicians make the best possible decisions," said AHRQ Director Carolyn M. Clancy, M.D. "This partnership with the FDA is a great way to move closer to answering important clinical questions that affect children and adults who have ADHD."

"Case reports have described adverse cardiovascular events in adult and pediatric patients with certain underlying risk factors who receive drug treatment for ADHD, but it is unknown whether or not these events are causally related to treatment," said Gerald Dal Pan, M.D., director of FDA's Office of Surveillance and Epidemiology. "The goal of this study is to develop better information on this question."

The study will be coordinated by Vanderbilt University researchers on contract through AHRQ's Effective Health Care program. Data analysis will be performed by researchers at Vanderbilt, Kaiser Permanente of California, the HMO Research Network and i3 Drug Safety, as well as from FDA and AHRQ. The analysis will include all drugs currently marketed for treating ADHD. The study will analyze the risks of all the drugs as a whole, and risks of the drugs grouped by class.

The analysis will take about two years to complete. Results are expected to be important not only to patients, their families and health care providers, but also to government insurance programs. Medicaid, Medicare, and the State Children's Health Insurance Program provide reimbursement for drugs prescribed for ADHD. This information could also be used to inform product labeling, which is used by health care providers when making treatment decisions.

ADHD is a behavioral disorder that, in many patients, causes hyperactivity, and may have a significant impact on school performance and social functioning. According to the National Institute of Mental Health, ADHD affects approximately 3 percent to 5 percent of school-age children and about 4 percent of adults.

Use of ADHD drugs has increased in recent years among children and adults. A recent AHRQ analysis of medication expenditures found three ADHD drugs—Concerta, Strattera, and Adderall—ranked among the top five drugs prescribed for children ages 17 years and younger. About $1.3 billion was spent on those drugs in 2004, the study estimated.  Adult use is also believed to be increasing.

In May 2006, based on a review of anecdotal reports of heart attack, stroke and sudden death among patients taking usual doses of ADHD medications, the FDA asked drug manufacturers to revise product labeling to reflect concerns about possible adverse events. Drug manufacturers have created patient Medication Guides for individual products to help patients understand risks.
FDA and AHRQ recommend that individuals using or being considered for treatment with ADHD drug products work with their physician or other health care professional to develop a treatment plan that includes a careful health history and evaluation of current health status, particularly for cardiovascular and psychiatric problems, including assessment for a family history of such problems.

For more information:

National Institute of Mental Health—ADHD page
www.nimh.nih.gov/healthinformation/adhdmenu.cfm

FDA News—ADHD Medications and Cardiovascular, Psychiatric Adverse Events
www.fda.gov/bbs/topics/NEWS/2007/NEW01568.html

AHRQ's Effective Health Care Program
www.effectivehealthcare.ahrq.gov

The U.S. Food and Drug Administration today cleared for marketing a new genetic test that will help physicians assess whether a patient may be especially sensitive to the blood-thinning drug warfarin (Coumadin), which is used to prevent potentially fatal clots in blood vessels.

One-third of patients receiving warfarin metabolize it quite differently than expected and experience a higher risk of bleeding. Research has shown that some of the unexpected response to warfarin depends on variants of two genes, CYP2C9 and VKORC1. The Nanosphere Verigene Warfarin Metabolism Nucleic Acid Test detects some variants of both genes.

"Today’s action offers physicians the first FDA cleared genetic test for warfarin sensitivity, which is another step in our commitment to personalized medicine,” said Daniel Schultz, M.D., director, FDA’s Center for Devices and Radiological Health. “With this test, physicians may be able to use genetic information along with other clinical information to treat their patients.”

Warfarin can be a difficult drug to use because the optimal dose varies depending on many risk factors, including a patient's diet, age, and the use of other medications. Rapidly achieving the correct dose is important. Patients who receive doses that are higher than needed to correctly thin the blood are at risk of life-threatening bleeding. Those who receive doses that are too low may remain at risk of life-threatening blood clots.

Warfarin is the second most common drug, after insulin, implicated in emergency room visits for adverse drug events.

In August, FDA approved updated labeling for Coumadin, the brand name version of warfarin, explaining that people with variations of the genes CYP2C9 and VKORC1 may respond differently to the drug. Manufacturers of generic warfarin are adding similar information to their products' labeling.

Physicians and other health care professionals who prescribe warfarin regularly check to see if the drug is working properly by ordering a test called the PT or prothrombin time that evaluates the blood's ability to clot properly. The results are measured in seconds and compared with the expected value in healthy people, known as the International Normalized Ratio or INR.

The Nanosphere test is not intended to be a stand-alone tool to determine optimum drug dosage, but should be used along with clinical evaluation and other tools, including INR, to determine the best treatment for patients.

FDA cleared the test based on results of a study conducted by the manufacturer of hundreds of DNA samples as well as on a broad range of published literature. In a three site study, the test was accurate in all cases where the test yielded a result; 8 percent of the tests could not identify which genetic variants were present.

The new test was cleared for use on the Verigene System, a clinical laboratory test system. Both products are manufactured by Nanosphere Inc., Northbrook, Ill.

The U.S. Food and Drug Administration has cleared for marketing the first rapid test to detect bacterial contamination in blood platelets prior to transfusion.

The Platelet Pan Genera Detection (PGD) Test System is a disposable test strip for use in a hospital transfusion service setting. It is intended to supplement current quality control testing methods used by blood establishments following collection of platelets using an automated instrument.

“The clearance of a rapid test is a significant step in the detection of bacterial contamination of platelets for transfusion,” said Jesse L. Goodman, M.D., M.P.H., director of FDA’s Center for Biologics Evaluation and Research. “In half an hour, a sample is prepared, processed and read, providing an additional assurance that the product is free from harmful bacteria.”

Platelets are used to prevent or treat bleeding in individuals undergoing chemotherapy for cancer, after major trauma, during or after surgery, and in individuals who do not produce platelets. Patients who are transfused with platelets contaminated with bacteria are at risk of developing a serious and potentially life-threatening infection of the blood stream known as blood poisoning. Blood poisoning must be treated quickly to prevent the infection from spreading to the heart and lungs.

Bacterial contamination of platelets is the leading infectious cause of transfusion-related patient fatalities. The risk of a patient receiving a transfusion contaminated with bacteria is 1 in 5,000 -- far greater than the risk of transmitting hepatitis C virus (1 in 1.6 million) or HIV (1 in 1.9 million). To reduce the risk of transfusing contaminated platelets, blood centers culture samples of the platelets 24 hours after the donation. The culture is read within the next 24 hours (within 48 hours after the donation), and contaminated units are discarded. However, there is a possibility that the number of bacteria present at the time of culture may be so low that bacteria is not detected due to sampling limitations.   
  
Rapid testing of blood platelets using the Platelet PGD Test System permits units of platelets to be retested at a time closer to their use. Although the test system is less sensitive than standard cultures, it is done later in storage when bacteria, if present, have multiplied, and thus are easier to detect.

The Platelet PGD Test System was developed by Verax Biomedica Inc., Worcester, Mass.

The U.S. Food and Drug Administration (FDA) today sent a warning letter to Procter & Gamble for making unlawful claims about its Vicks Early Defense Foaming Hand Sanitizer (Early Defense) product.

The agency says the product’s claims and directions for use cause it to be an unapproved new drug under the Federal Food, Drug, and Cosmetic Act. It cited specifically Procter & Gamble promotion of Early Defense for use by schoolchildren to prevent colds and to provide antimicrobial activity for up to three hours. Although FDA is not aware of significant health risks associated with Early Defense, the agency is concerned because this product has not been proven safe and effective for these claims.

“FDA is concerned with the marketing of this over-the-counter drug for use by school children and others,” said Steven K. Galson, M.D., M.P.H., director of FDA’s Center for Drug Evaluation and Research. “Over-the-counter (OTC) drugs are often widely used without supervision by a doctor or other health care professional, so it is essential that manufacturers obtain FDA approval or fully comply with OTC monographs and agency policies.”

Under its OTC drug monograph system, FDA allows OTC drugs to be marketed without first obtaining agency approval in certain circumstances. These drugs must comply with applicable standards regarding monographs that specify conditions for the drugs’ labeling and formulation. OTC drugs that do not have FDA approval and do not meet these requirements are considered unapproved drugs that are unlawfully marketed.

There is a proposed OTC monograph that covers triclosan, the active ingredient in Early Defense. FDA allows companies to market their products (which would otherwise be unapproved new drugs) under proposed monographs, as long as the companies comply with the conditions in the proposed monograph. In this case, the product's claims that it prevents colds and provides up to three hours of antimicrobial activity are not allowed under the proposed monograph. Under the proposed monograph, when antimicrobial products use triclosan as their active ingredient, their labeling must direct consumers to rinse with water after use and Early Defense does not. Early Defense falls outside the proposed monograph and is considered an unapproved new drug because it lacks these directions and makes these impermissible claims.

FDA regards compliance with its approval and monograph requirements to be integral to drug safety. Without the foundation of compliance, it is not possible to ensure that consumers and the health care community are provided with established and emerging drug safety information so that they can make the best possible medical decisions about the safe and effective use of drugs.

Companies that do not resolve violations in FDA warning letters risk enforcement actions, such as injunctions against continuing violations and seizure of illegal products.For a copy of the warning letter, visit: http://www.fda.gov/foi/warning_letters/s6508c.htm

For more information on FDA’s Drug Safety Initiative, visit:
http://www.fda.gov/cder/drugSafety.htm

The U.S. Food and Drug Administration (FDA) has named Timothy Coté, M.D., M.P.H., as the new director of FDA's Office of Orphan Products Development. Dr. Coté will be responsible for promoting the development of products that demonstrate promise for the diagnosis or treatment of rare diseases or conditions.

"We are very pleased to have Dr. Coté rejoin the FDA as the new head of the Orphan Products Development office," said Janet Woodcock, M.D. deputy commissioner for the FDA. "Tim brings a plethora of experience confronting emerging health issues in the United States and abroad, coupled with a commitment to public service."

Dr. Coté's experience ranges from medical epidemiology to clinical research.

Dr. Coté, a captain in the U.S. Public Health Service Commissioned Corps, most recently served as the Centers for Disease Control's (CDC) country director for the African nation of Rwanda. In Rwanda, he directed programs in HIV/AIDS, malaria and avian influenza, and was responsible for scientific and administrative leadership in patient care and research initiatives. He also oversaw the President's Emergency Plan for AIDS Relief (PEPFAR) operations in Rwanda. Under his leadership, the numbers of HIV-infected individuals receiving anti-retroviral medications from the United States rose from 20,000 to 55,000 persons.

Early in his career, he was a CDC Epidemic Intelligence Officer at the Maryland Health Department. He also served as a senior federal advisor for CDC at the District of Columbia Health Department. From February 2002 until August 2004 Dr. Coté was the chief of the Therapeutics and Blood Safety Branch in the FDA's Center for Biologics Evaluation and Research, Office of Biostatistics and Epidemiology.

Dr. Coté has a bachelor of arts degree in biology and psychology from Syracuse University. He earned his medical degree from Howard University College of Medicine, and a masters in public health from the Harvard School of Public Health. Dr. Coté also volunteers as a general practitioner for the Spanish Catholic Center in Wheaton, Md.