Orphan drug becomes first of its kind to treat this genetic disorder
The U.S. Food and Drug Administration today approved Kuvan (sapropterin dihydrochloride), the first drug of its kind approved to slow the effects of a rare genetic disorder that causes mental retardation, smaller brain size, delayed speech and other neurological problems. Tetrahydrobiopterin (BH4)-responsive phenylketonuria or PKU disease occurs in one out of every 12,000 to 15,000 live births in the United States.

PKU is a genetic disorder in which the enzyme phenylalanine hydroxylase (PAH), which helps our bodies break down phenylalanine (Phe), an amino acid found in foods, does not function properly. The result is high levels of phenylalanine in the blood. High levels of Phe are toxic to the brain and can lead to mental retardation, behavioral abnormalities, seizures, an inability to focus and organize information, and other neurologic complications.

“This new drug therapy represents hope for patients and families dealing with this difficult disease,” said Janet Woodcock, M.D., FDA’s deputy commissioner for scientific and medical programs, chief medical officer, and acting director of the Center for Drug Evaluation and Research. “Now, for the first time, there is a medical intervention to help patients and their families slow the devastating neurological effects of this disease.”

Kuvan was first granted orphan drug designation by the FDA in January 2004. A drug is eligible for orphan drug designation if it is intended to treat a disease or condition that affects less than 200,000 people in the United States. A drug is also eligible for orphan drug designation if it is intended to treat a disease of condition that affects more than 200,000 and there is no reasonable expectation that the cost of developing and making available a drug for the disease or condition will be recovered from sales of the drug.

In January, 2006 Kuvan was granted a fast track designation by FDA based on its potential to offer a significant advantage to patients over current treatment options. The Kuvan new drug application (NDA) also received a priority review by FDA.

Kuvan works by increasing PAH enzyme activity in PKU patients with some residual PAH enzyme function. This then leads to an increased breakdown (metabolism) of phenylalanine (Phe), resulting in lower levels of Phe in the blood.

Kuvan must be used in combination with a phenylalanine-restricted diet. A patient can override the effects of Kuvan by not following a Phe-restricted diet. Phenylalanine is present in foods that contain proteins such as meats, dairy and egg products.

Patients being treated with Kuvan must have their blood phenylalanine levels monitored frequently by their physicians or other health care professional to ensure their Phe levels are in the normal range. FDA also recommends patients work closely with a dietitian to manage their diets. In addition, the manufacturer will establish general disease registries for PKU to help FDA and physicians track how patients are doing on the medication around the world in order to monitor its safety, efficacy and any adverse events.
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The safety and efficacy of Kuvan was demonstrated in four short-term (up to 30 weeks) clinical studies with 579 patients with the disease. The data from these studies supported the clinical effectiveness of Kuvan in the treatment of BH4-responsive PKU. The most common adverse events reported included headache, diarrhea, abdominal pain, upper respiratory tract infection and throat pain.

Kuvan was developed by BioMarin Pharmaceutical Inc. based in Novato, Calif. in partnership with Merck Serono, a division of Merck KGaA, Darmstadt, Germany.


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Deaths and serious injuries from improper
The Food and Drug Administration today issued its second safety warning about the fentanyl transdermal system, an adhesive patch that delivers a potent pain medicine through the skin. In July 2005, the agency issued a similar warning to the public and to health care providers, saying that the directions on the product label and on the patient package insert should be followed exactly in order to avoid overdose. FDA has continued to receive reports of deaths and life-threatening side effects after doctors have inappropriately prescribed the patch or patients have incorrectly used it.   

In addition, the agency is asking manufacturers of all fentanyl patches to update their product information and to develop a medication guide for patients.

The fentanyl skin patch contains the opioid fentanyl, a potent narcotic. The skin patch was approved by FDA in 1990 for use in patients with persistent, moderate-to-severe pain who have become opioid tolerant – meaning that they have been using another strong opioid narcotic pain medicine around-the-clock, and have been using the medicine regularly for a week or longer. The skin patch is most commonly prescribed for patients with cancer.

Recent reports to FDA describe deaths and life-threatening side effects after doctors and other health care professionals inappropriately prescribed the patch to relieve pain after surgery, for headaches, or for occasional or mild pain in patients who were not opioid tolerant. In other cases, patients used the patch incorrectly: The patients replaced it more frequently than directed in the instructions, applied more patches than prescribed, or applied heat to the patch – all resulting in dangerously high fentanyl levels in the blood.

“There is an unmet need to provide patients suffering from chronic pain with safe and effective products that will not only alleviate their pain, but that will also be tolerable when used chronically,” said Bob Rappaport, M.D., FDA’s director of the Division of Anesthesia, Analgesia and Rheumatology Products. "While these products fill an important need, improper use and misuse can be life-threatening. Therefore, it is crucial that doctors prescribe these products appropriately and that patients use them correctly."

In its Public Health Advisory and Health Care Professional Sheet published today, FDA stressed the following safety information:

Fentanyl patches are only for patients who are opioid-tolerant and have chronic pain that is not well controlled with other pain medicines. The patches are not to be used to treat sudden, occasional or mild pain, or pain after surgery.  
Health care professionals who prescribe the fentanyl patch, and patients who use it, should be aware of the signs of fentanyl overdose: trouble breathing or slow or shallow breathing; slow heartbeat; severe sleepiness; cold, clammy skin; trouble walking or talking; or feeling faint, dizzy, or confused. If these signs occur, patients should get medical attention right away.
Patients prescribed the fentanyl patch should tell their doctor, pharmacist and other health care professionals about all the medicines that they take. Some medicines may interact with fentanyl, causing dangerously high fentanyl levels in the blood and life-threatening breathing problems.
Patients and their caregivers should be told how to use fentanyl patches. This important information, including instructions on how often to apply the patch, reapplying a patch that has fallen off, replacing a patch, and disposing of the patch, is provided in the patient information that comes with the fentanyl patch.
Heat may increase the amount of fentanyl that reaches the blood and can cause life-threatening breathing problems and death. Patients should not use heat sources such as heating pads, electric blankets, saunas, or heated waterbeds or take hot baths or sunbathe while wearing a patch. A patient or caregiver should call the patient’s doctor right away if the patient has a temperature higher than 102 degrees while wearing a patch.
This information will be reflected in the updated product information new medication guides for patients that manufacturers are being asked by FDA to develop.

The fentanyl skin patch is marketed under the brand name Duragesic by Johnson and Johnson, and generic versions of the product are sold by other manufacturers.

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Effort part of Food Protection Plan for ensuring the safety of domestic and imported foods eaten by American consumers
As part of the FDA’s comprehensive Food Protection Plan initiative, the agency today released self-assessment tools for industry to minimize the risk of intentional contamination of food and cosmetics. The tools are companion pieces designed to make previously issued industry guidance documents more user-friendly and practical.

Food protection is one of FDA’s top priorities and that means guarding against both intentional and unintentional contamination of foods. “The tools FDA is providing will help members of the food and cosmetic industry identify opportunities to better guard against intentional contamination of their products,” said CFSAN  Acting Center Director David Acheson.

In 2003, FDA issued a set of Food and Cosmetic Security Preventive Measures Guidance documents. These documents are aimed at operators of food and cosmetic establishments, as well as businesses that produce, process, store, repack, relabel, distribute, sell or transport foods, food ingredients, and cosmetics to help them minimize the risk of malicious, criminal, or terrorist actions involving products under their control.

The guidance documents are:

Food Producers, Processors, and Transporters: Food Security Preventive Measures Guidance
Importers and Filers: Food Security Preventive Measures Guidance
Retail Food Stores and Food Service Establishments: Food Security Preventive Measures Guidance
Cosmetics Processors and Transporters: Cosmetics Security Preventive Measures Guidance
Dairy Farms, Bulk Milk Transporters, Bulk Milk Transfer Stations and Fluid Milk Processors Food Security Preventive Measures Guidance
Using feedback from industry, the FDA repackaged the information found in the guidance documents and created a corresponding self-assessment tool for each document. By using the tools, industry members can get a quick and detailed assessment of the measures they currently have in place to protect against intentional contamination of their products. With this consolidated information, it will be easy for them to see where meaningful improvements to their current practices can be made.

The self-assessment tool asks the participant to mark the presence of a variety of food protection measures with a Y (Yes), N (No), N/A (Not Applicable), or Don't Know for each item. Examples of measures addressed by the self-assessment tools include the possibility of product tampering; identification of security procedures and responsibilities; and evaluation of response strategies in the event of product tampering or other intentional contamination.

For more information

The Food and Cosmetic Security Preventive Measures Guidance documents and self assessment tools http://www.cfsan.fda.gov/~dms/defguids.html

The Food Protection Plan
http://www.fda.gov/oc/initiatives/advance/food/plan.html.

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New Era Canning Company Voluntarily Recalls Product
The U.S. Food and Drug Administration (FDA) is warning consumers about a potential Clostridium botulinum  (C. botulinum) contamination of canned cut green beans manufactured by New Era Canning Company, New Era, Mich., and labeled as "GFS Fancy Blue Lake Cut Green Beans." C. botulinum is the bacterium that causes botulism.

The bacterium produces a toxin that can result in a life-threatening illness or death. To date, no illnesses have been reported in connection with this incident.  

The canned cut green beans were distributed to retailers, restaurants and foodservice institutions by Gordon Food Service, Grand Rapids, Mich., with lot code 19H7FL and UPC code 93901 11873, in large institutional-sized, 6 pound 5 ounce (#10) cans.  The green beans were distributed to food service customers in Alabama, Arkansas, Georgia, Illinois, Indiana, Kentucky, Mississippi, Missouri, North Carolina, Tennessee, and Virginia and sold through GFS Marketplace stores in Indiana, Kentucky, and Tennessee. There is no evidence of primary distribution outside the United States.

Customers who have the affected cans of cut green beans or who have used the green beans in recipes should throw cans and food away immediately. Any food that may be contaminated should be disposed of carefully. Even tiny amounts of the C. botulinum toxin ingested, inhaled, or absorbed through the eye or a break in the skin can cause serious illness. Skin contact should be avoided as much as possible, and the hands should be washed immediately after handling the food.

When disposing of this product, double-bag the cans in plastic bags.  Make sure the bags are tightly closed, then place in a trash receptacle for non-recyclable trash outside of the home.  Restaurants and institutions should ensure that such products are only placed in locked receptacles that are not accessible to the public. Additional instructions for safe disposal may be found at www.cdc.gov/ncidod/dbmd/diseaseinfo/botulism_g.htm.  Anyone with questions can call FDA at 1-888-SAFEFOOD.

As part of this ongoing investigation, FDA is working closely with Michigan Department of Agriculture state officials and New Era to identify all products that may be involved.  Michigan Department of Agriculture, under its state authority, seized most canned products in the company's warehouses. New Era is voluntarily recalling 171 cases of the green beans (6 cans per case).  

Symptoms of botulism poisoning in humans can begin from 6 hours to 2 weeks after eating food that contains the toxin. Symptoms may include double vision, blurred vision, drooping eyelids, slurred speech, difficulty swallowing, and muscle weakness that moves progressively down the body, affecting the shoulders first, then descending to the upper arms, lower arms, thighs, and calves. Botulism poisoning also can cause paralysis of the breathing muscles, which can result in death unless assistance with breathing (mechanical ventilation) is provided. Individuals who have these symptoms and who may have recently eaten the cut green beans currently under recall or other food products made with these green beans should seek immediate medical attention.  

FDA learned of the potential contamination on Dec. 20, when testing of product collected during an FDA inspection showed a presumptive positive result for C. botulinum. This incident illustrates the important health protection role that FDA inspections play and the need for firms to have adequate preventive control systems in place.  Prevention of foodborne illness is a key element of the FDA's new Food Protection Plan, launched November 6, 2007.

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The FDA yesterday released a ruling that instructed manufacturers of spermicide gels, sold without prescripton, that contain nonoxynol- 9 to include a warning stating that the products do not protect against HIV.

In fact, clinical evidence has shown that these topical gels actually increase the risk of HIV transmission.

N-9 was one of the first microbicides to inspire hope as a potentially cheap, easy to use addition to the HIV arsenal, since, in laboratory tests, the it kills the HIV virus and other common sexually transmitted infections.

But as far back as 1998, questions started to be asked about its ability to protect against STIs in a clinical setting.

In one dramatic disappointment, a phase III trial carried out in Africa, the results of which were released in 2000, showed that the use of N-9 products could increase the risk of HIV transmission by up to 50 per cent. The researchers’ analysis of the data collected during the trial revealed that, the more frequently women used only N-9 gel (without a condom) to protect themselves, the higher their risk of becoming infected. This is probably because the gel caused irritation of mucous membranes.

Manufacturers of these products do not endorse them as stand-alone protection against sexually transmitted diseases, but it has taken almost eight years to transfer clinical data into a simple warning label. It’s already more than three years since the FDA proposed the warning in the first place, according to a Reuters report.

One-a-day HIV drugs:
Bristol-Myers Squibb and Gilead Sciences have received EU approval of Atripla, their one-a-day combination HIV drug, before the end of 2007. The treatment, which is already approved in the US and Canada, combines BMS’s antiretroviral Sustiva (efavirenz) with Gilead drugs Emtriva (emtricitabine) and Viread (tenofovir disoproxil fumarate). Atripla is the first once-daily, single tablet treatment for HIV in the EU.

Galvus closes in on EU approval:
Novartis has received European backing for a low-dose prescriptions of type 2 diabetes drug Galvus. The medicine initially received EU approval, in 50mg and 100mg doses, in September 2007, but in November Novartis delayed the launch after concerns over the liver safety of the higher dose. The European Committee for Medicinal Products for Human Use has issued a positive opinion on 50mg doses of the drug, and full EU approval is expected within three months. Like Merck’s already approved Januvia, Galvus doesn’t cause weight gain, a common side effect of earlier diabetes drugs.

Test Identifies MRSA Bacterium in Two Hours
The U.S. Food and Drug Administration (FDA) today announced it has cleared for marketing the first rapid blood test for the drug-resistant staph bacterium known as MRSA (methicillin-resistant Staphylococcus aureus), which can cause potentially deadly infections.

Methicillin is an antibiotic that has been used successfully to treat infections from the Staphylococcus aureus bacterium. Over the years, the staph bacterium mutated and spawned MRSA, a strain of staph bacterium that is resistant to methicillin and which has a higher rate of being fatal.

The BD GeneOhm StaphSR Assay uses molecular methods to identify whether a blood sample contains genetic material from the MRSA bacterium or the more common, less dangerous staph bacterium that can still be treated with methicillin.

“The BD GeneOhm test is good news for the public health community. Rather than waiting more than two days for test results, health care personnel will be able to identify the source of a staph infection in only two hours, allowing for more effective diagnosis and treatment,” said Daniel G. Schultz, M.D., director, FDA’s Center for Devices and Radiological Health.

Staph infections occur most frequently among persons in hospitals and health care facilities (such as nursing homes and dialysis centers) who have weakened immune systems. Both types of bacteria also can infect healthy people.

Distinguishing between the two sources of infection is critical to successful treatment.
The more common, less dangerous strain of staph results in infections that are generally mild and affect the skin with pimples or boils that can be swollen, painful and drain pus.

However, the MRSA staph bacterium is difficult to treat with ordinary antibiotics. It can cause potentially life-threatening conditions such as blood stream infections, surgical site infections or pneumonia.

FDA cleared the BD GeneOhm StaphSR assay based on the results of a clinical trial at five locations. The new assay identified 100 percent of the MRSA-positive specimens and more than 98 percent of the more common, less dangerous staph specimens.

In order to preserve the integrity of positive test results, this test should be used only in patients suspected of a staph infection. The test should not be used to monitor treatment for staph infections because it cannot quantify a patient’s response to treatment. Test results should not be used as the sole basis for diagnosis as they may reflect the bacteria’s presence in patients who have been successfully treated for staph infections. Also, the test will not rule out other complicating conditions or infections.

The BD GeneOhm StaphSR test is manufactured by BD Diagnostics, a subsidiary of BD of Franklin Lakes, N.J.

Consistent With Previous Data on Tumor Growth and Death
The U.S. Food and Drug Administration (FDA) is reviewing new data from two studies that provide further evidence of the risks of anemia drugs known as erythropoiesis-stimulating agents, or ESAs. The studies show that patients with breast or advanced cervical cancers who received ESAs to treat anemia caused by chemotherapy died sooner or had more rapid tumor growth than similar patients who didn’t receive the anemia drug.

These two studies were not among the six studies that were described in revised labeling approved by FDA Nov. 8, 2007, which strengthened warnings about ESAs in cancer patients.

Taken together, all eight studies show more rapid tumor growth or shortened survival when patients with breast, non-small cell lung, head and neck, lymphoid or cervical cancers received ESAs compared to patients who did not receive this treatment. In all of these recent studies, ESAs were administered in an attempt to achieve a hemoglobin level of 12 grams per deciliter (g/dL) or greater, although many patients did not reach that level.

FDA plans to discuss this new data and revisit the risks and benefits of using ESAs in patients with chemotherapy-induced anemia at a public advisory committee meeting in the next few months.

“This new information further underscores the safety concerns regarding the use of ESAs in patients with cancer, which FDA addressed in previous communications,” said Janet Woodcock, M.D., FDA's deputy commissioner for scientific and medical programs, chief medical officer, and acting director of the Center for Drug Evaluation and Research.

“FDA is reviewing these data and may take additional action. In the meantime, FDA recommends that health care providers review the risks and benefits of ESAs outlined in the product label and discuss this information with their patients.”

ESAs are a bioengineered version of a natural protein made in the kidney that stimulates the bone marrow to produce more red blood cells.

Physicians determine whether a patient is anemic and decide on ESA dosing by measuring how much of the protein known as hemoglobin is present in a patient's red blood cells, typically expressed in grams per deciliter.

FDA-approved uses of ESAs are for the treatment of anemia in patients with chronic kidney failure; for cancer patients whose anemia is caused by chemotherapy; and for those infected with the human immunodeficiency virus (HIV) whose anemia is caused by the HIV drug AZT (zidovudine). ESAs are also approved to reduce the number of transfusions during and after major surgery.

On Nov. 30, Amgen, manufacturer of the three ESAs -- Aranesp, Epogen, and Procrit -- provided FDA with information from the 733-patient PREPARE study of women who received chemotherapy before undergoing surgery for breast cancer. After three years, 14 percent of the patients who received Aranesp to treat their anemia had died, compared to 9.8 percent who did not receive the drug. Tumor growth was also faster in patients receiving Aranesp.

On Dec. 4, Amgen informed FDA of the results of a study by the National Cancer Institute’s Gynecologic Oncology Group of patients receiving chemotherapy and radiation for advanced cervical cancer. The patients were administered either Procrit to maintain hemoglobin levels above 12 g/dL or blood transfusions as needed. After three years, 66 percent of the patients who did not take Procrit were alive and free of cancer growth compared to 58 percent who had received the drug.

FDA approved revised boxed warnings and other safety-related product labeling changes for ESAs in November and March 2007. Safety concerns regarding ESAs were discussed during advisory committee meetings in 2004 and 2007 and labeling was revised in 1997, 2004 and 2005 to reflect new safety information

This communication is in keeping with FDA's commitment to inform the public about its ongoing safety reviews. FDA is committed to strengthening the science that supports medical product safety at every stage of the product life cycle from pre-market testing and development through post-market surveillance and risk management.

Amgen is based in Thousand Oaks, Calif. Procrit is marketed and distributed by Ortho Biotech LP of Bridgewater, N.J, a subsidiary of Johnson & Johnson.

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The U.S. Food and Drug Administration today cleared for marketing a test that simultaneously detects and identifies 12 specific respiratory viruses.

The test, called the xTAG Respiratory Viral Panel, is the first test for the detection and differentiation of influenza A subtypes H1 and H3. Influenza A is the most severe form of influenza for humans, and has been the cause of major epidemics. The new panel is also the first test for human metapneumovirus (hMPV), newly identified in 2001.

The xTAG Respiratory Viral Panel amplifies viral genetic material found in secretions taken from the back of the throat in patients with possible respiratory tract infections. In the test, specific beads, or microspheres, bind to the amplified viral genetic material. The beads are then sorted so that the specific virus can be identified.

The xTAG panel is the first FDA-cleared test for infectious respiratory disease viruses that uses a multiplex platform, allowing several tests to be processed using the same sample.

"Nucleic acid tests such as the xTAG Respiratory Viral Panel utilize small amounts of genetic material, and then replicate it many times," said Daniel G. Schultz, M.D., director of FDA's Center for Devices and Radiological Health.

"This speeds up the usual process of detecting and identifying respiratory viruses, which can take up to a week," said Schultz. "And, because this multiplex viral panel tests for 12 viruses at once, it uses less of a patient's test specimen."

Other viruses identified by the xTAG Respiratory Viral Panel:

influenza B - one of three types of human influenza, less severe than influenza A
respiratory syncytial virus subtype A and B – both are leading causes of infant pneumonia and bronchiolitis (an infection of the airways leading to the lungs) and often contribute to the development of long-term pulmonary disease
parainfluenza 1, 2 and 3 – all are leading factors in the croup and the common cold
rhinovirus – the most common viral infective agent in humans and a cause of the common cold
adenovirus – a cause of respiratory tract infections often similar to strep throat or tonsilitis
While the test is faster than conventional tests, it is specific to the dozen viruses listed and should be used with other diagnostics such as patient data, bacterial or viral cultures and X-rays. Positive results do not rule out other infection or co-infection and the virus detected may not be the specific cause of the disease or patient symptoms.

The xTAG Respiratory Viral Panel is manufactured by Toronto-based Luminex Molecular Diagnostics

Commissioner of Food and Drugs Andrew C. von Eschenbach, M.D., is pleased to announce two major changes in the agency's senior leadership team. Effective Monday, Stephen F. Sundlof, D.V.M., Ph.D., is moving from director of FDA's Center for Veterinary Medicine (CVM) to director of FDA's Center for Food Safety and Applied Nutrition (CFSAN). Bernadette Dunham, D.V.M., Ph.D., who is deputy director of CVM, will assume directorship of CVM, also effective Monday.

"It is more important than ever that the American public feel confident in the safety of the food they eat and feed their loved ones," said von Eschenbach. "Drs. Sundlof and Dunham are world class scientists and leaders, with the dedication, vision and expertise needed to tackle challenges and enhance the science involved in assuring the safety and nutritional value of something so vital to healthy life; namely our food."

For over a decade, Dr. Sundlof has served as the director of CVM. In that capacity, with his background as a toxicologist, he has overseen the regulation of feed, including food additives, and drugs intended for animals. These include animals from which human foods are derived, as well as food and drugs for pets (or companion animals) and other non-food-producing animals such as zoo animals, parakeets, hamsters, and aquarium fish.

Dr. Sundlof has extensive experience in the food safety and protection arena, including service on numerous domestic and international committees on food safety, where he served as chairman and led the development of new international policies and safety standards. He also provided significant input into the development of the FDA's Food Protection Plan issued in November 2007, a strategic and comprehensive approach to improve food safety and defense in the United States. He was instrumental in putting in place robust animal feed programs to prevent Bovine Spongiform Encephalopathy (BSE), also called mad cow disease, from entering the U.S. feed system. There have been no cases of mad cow disease in the United States resulting from a failure of the feed system. This depth and breadth of experience makes him well suited to serve as director of CFSAN.

Prior to joining FDA, Dr. Sundlof served on the faculty of the College of Veterinary Medicine, University of Florida, where he held the rank of professor of toxicology. He also has received many honors and awards as a leader in his field and has authored several scientific and technical papers. Since 1994 he has served as chairman of the Codex Committee on Residues of Veterinary Drugs in Foods.

Dr. Dunham has worked closely with Dr. Sundlof in her role as deputy director of CVM since 2006. She has played a critical role, and provided executive leadership, in coordinating and establishing center policy in research, management, scientific evaluation, compliance, and surveillance. While serving as CVM deputy director, Dr. Dunham also was the director for CVM's Office of Minor Use and Minor Species Animal Drug Development, the office that oversees drug development for minor species, such as zoo animals, ornamental fish, parrots, ferrets, guinea pigs, sheep, goats, catfish, and honeybees. That office also oversees drug development for uncommon diseases in major species, such as cattle, pigs, chicken, turkeys, horses, dogs and cats.

Before joining the FDA in 2002, Dr. Dunham served in several important leadership positions with the American Veterinary Medical Association and held faculty positions at several universities, including at the Department of Pharmacology at the State University of New York Health Science Center (SUNY-HSC) at Syracuse, while concurrently acting as the director of laboratory animal medicine at SUNY-HSC at Syracuse.

In addition to the scientific peer recognition she has received throughout her career, Dr. Dunham continues to collaborate with colleagues outside of FDA, as evidenced by her two FDA Leveraging/Collaboration Awards. One recognized her accomplishments as a member of the Swissmedic Bilateral Collaboration, through which the FDA and its Swiss counterpart work to increase collaboration on facility inspections. The other acknowledged her contributions to the U.S.-Canada-Mexico Security and Prosperity Partnership/Negotiation Team. This partnership is a trilateral effort to increase security and enhance prosperity among the United States, Canada and Mexico through greater cooperation and information sharing.

Drs. Sundlof and Dunham will report directly to Dr. von Eschenbach.