The U.S. Food and Drug Administration (FDA)'s Nanotechnology Task Force today released a report that recommends the agency consider developing guidance and taking other steps to address the benefits and risks of drugs and medical devices using nanotechnology.

"Nanotechnology holds enormous potential for use in a vast array of products," said Commissioner of Food and Drugs Andrew von Eschenbach, M.D., who endorsed the Task Force Report and its recommendations on July 23, 2007. "Recognizing the emerging nature of this technology and its potential for rapid development, this report fosters the continued development of innovative, safe and effective FDA-regulated products that use nanotechnology materials."

Scientists and researchers increasingly are working in the nanoscale, creating and using materials and devices at the level of molecules and atoms—1/100,000th the width of a human hair.

The FDA's Task Force Report on Nanotechnology addresses regulatory and scientific issues and recommends FDA consider development of nanotechnology-associated guidance for manufacturers and researchers. The Task Force was initiated by Commissioner von Eschenbach in 2006.

The Task Force reports that nanoscale materials potentially could be used in most product types regulated by FDA and that those materials present challenges similar to those posed by products using other emerging technologies. The challenges, however, may be complicated by the fact that properties relevant to product safety and effectiveness may change as size varies within the nanoscale.

The report also says that the emerging and uncertain nature of nanotechnology and the potentially rapid development of applications for FDA-regulated products highlight the need for ensuring transparent, consistent, and predictable regulatory pathways.

Anticipating the potential for rapid development in the field, the report recommends consideration of agency guidance that would clarify, for example, what information to give FDA about products, and also when the use of nanoscale materials may change the regulatory status of particular products. As with other FDA guidance, draft guidance documents would be made available for public comment prior to being finalized.

In addition, the report says the FDA should work to assess data needs to better regulate nanotechnology products, including biological effects and interactions of nanoscale materials. The agency also should develop in-house expertise and ensure consideration of relevant new information on nanotechnology as it becomes available, according to the report. FDA should evaluate the adequacy of current testing approaches to assess safety, effectiveness and quality of nanoscale materials.

FDA and 22 other federal agencies are part of the National Nanotechnology Initiative, a federal research and development program established to coordinate the multi-agency efforts in nanoscale science, engineering, and technology.

For more information:

FDA Nanotechnology Report

Report PDF: www.fda.gov/nanotechnology/taskforce/report2007.pdf

Report HTML: www.fda.gov/nanotechnology/taskforce/report2007.html

Consumer Article: www.fda.gov/consumer/updates/nanotech072507.html

National Nanotechnology Initiative: http://www.nano.gov/

Fact sheet: http://www.fda.gov/nanotechnology/taskforce/factsheet2007.html

FDA Statement on Gene Therapy Clinical Trial
On July 24, 2007 the U.S. Food and Drug Administration (FDA) was informed by Targeted Genetics Corporation of Seattle about the death of a patient who received an investigational gene therapy product in a clinical trial for the treatment of active inflammatory arthritis.

FDA's condolences go to the patient's family.

FDA is providing this preliminary information in recognition of the public's interest in these types of new therapies.

Targeted Genetics notified FDA earlier that a patient in its trial experienced a serious adverse event. Even though the cause of the illness wasn't known, and is still uncertain, the agency immediately placed the trial on clinical hold--meaning no further product can be administered and no new patients can be enrolled.

The product that was being studied uses a particle called a vector that is designed to deliver treatment genes to target cells. The vector used is a recombinant adeno-associated virus (AAV) derived vector and delivers the gene for Tumor-Necrosis Factor -Receptor, with the intent to inhibit a key mediator of inflammation. In the study, the gene therapy was administered into the joint affected by the disease to reduce inflammation and disease in patients with active inflammatory arthritis.

More than 100 subjects have been enrolled in the trial, according to the company, without known similar serious events. However, the patient's illness was related in time to the receipt of a second injection of the product. Upon being alerted to the adverse event, FDA immediately began its investigation to determine whether the illness was related to the treatment. The investigation into the cause of the patient's illness and subsequent death is intensive and ongoing.

Targeted Genetics is cooperating with FDA's investigation and has agreed to provide the agency with ongoing results from various tests and all other information it is compiling that may help determine the cause of this patient's death. FDA is also coordinating with the National Institutes of Health in an effort to acquire a better understanding of the potential scientific and safety implications of this event. These matters will be discussed at the September meeting of the NIH Recombinant DNA Advisory Committee.

FDA is not aware of similar adverse events occurring in other gene therapy trials either with this specific product or with those that use other genes in AAV vectors. However, as a precaution, the agency is further reviewing all ongoing trials involving any use of AAV.

FDA recognizes the contributions of participants in clinical trials and places a high priority on potential safety issues – volunteers play a critical role in making treatments available that have the potential to help many other patients who need new treatments for serious diseases.
The agency is continuing to obtain and assess additional information to help determine, if possible, the cause of the event, and any potential implications and will take additional steps and provide updates as warranted.

On July 24, 2007 the U.S. Food and Drug Administration (FDA) was informed by Targeted Genetics Corporation of Seattle about the death of a patient who received an investigational gene therapy product in a clinical trial for the treatment of active inflammatory arthritis.

FDA's condolences go to the patient's family.

FDA is providing this preliminary information in recognition of the public's interest in these types of new therapies.

Targeted Genetics notified FDA earlier that a patient in its trial experienced a serious adverse event. Even though the cause of the illness wasn't known, and is still uncertain, the agency immediately placed the trial on clinical hold--meaning no further product can be administered and no new patients can be enrolled.

The product that was being studied uses a particle called a vector that is designed to deliver treatment genes to target cells. The vector used is a recombinant adeno-associated virus (AAV) derived vector and delivers the gene for Tumor-Necrosis Factor -Receptor, with the intent to inhibit a key mediator of inflammation. In the study, the gene therapy was administered into the joint affected by the disease to reduce inflammation and disease in patients with active inflammatory arthritis.

More than 100 subjects have been enrolled in the trial, according to the company, without known similar serious events. However, the patient's illness was related in time to the receipt of a second injection of the product. Upon being alerted to the adverse event, FDA immediately began its investigation to determine whether the illness was related to the treatment. The investigation into the cause of the patient's illness and subsequent death is intensive and ongoing.

Targeted Genetics is cooperating with FDA's investigation and has agreed to provide the agency with ongoing results from various tests and all other information it is compiling that may help determine the cause of this patient's death. FDA is also coordinating with the National Institutes of Health in an effort to acquire a better understanding of the potential scientific and safety implications of this event. These matters will be discussed at the September meeting of the NIH Recombinant DNA Advisory Committee.

FDA is not aware of similar adverse events occurring in other gene therapy trials either with this specific product or with those that use other genes in AAV vectors. However, as a precaution, the agency is further reviewing all ongoing trials involving any use of AAV.

FDA recognizes the contributions of participants in clinical trials and places a high priority on potential safety issues – volunteers play a critical role in making treatments available that have the potential to help many other patients who need new treatments for serious diseases.
The agency is continuing to obtain and assess additional information to help determine, if possible, the cause of the event, and any potential implications and will take additional steps and provide updates as warranted.

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The U.S. Food and Drug Administration announced that it is permitting the restricted use of Zelnorm (tegaserod maleate) under a treatment investigational new drug (IND) protocol to treat irritable bowel syndrome with constipation (IBS-C) and chronic idiopathic constipation (CIC) in women younger than 55 who meet specific guidelines.

In some instances, patients with a serious or life-threatening disease or condition who are not enrolled in a clinical trial may be treated with a drug not approved by the FDA. Generally, such use is allowed within guidelines called a treatment IND, when no comparable or satisfactory alternative drug or therapy is available.

In addition to the age and gender restrictions, the IND protocol for Zelnorm limits use of the drug to those with IBS-C or CIC whose physicians decide the drug is medically necessary. Patients must sign consent materials to ensure they are fully informed of the potential risks and benefits of Zelnorm.

On March 30, 2007, the FDA asked Novartis, the manufacturer of Zelnorm, to suspend its U.S. marketing and sales because a safety analysis found a higher chance of heart attack, stroke, and unstable angina (heart/chest pain) in patients treated with Zelnorm compared with treatment with an inactive substance (placebo).

At that time, the FDA indicated that there might be patients for whom the benefits of Zelnorm treatment outweigh the risks and for whom no other treatment options were available. FDA committed to work with Novartis to allow access to Zelnorm for those patients through a special program. That work yielded this IND protocol.

"These patients must meet strict criteria and have no known or pre-existing heart problems and be in critical need of this drug," said Steven Galson, M.D., M.P.H., director of FDA's Center for Drug Evaluation and Research (CDER). "Zelnorm will remain off the market for general use."

Irritable bowel syndrome is a disorder characterized most commonly by cramping, abdominal pain, bloating, constipation, and diarrhea. IBS causes a great deal of discomfort and distress, but it does not permanently harm the intestines and does not lead to disease. For some people, however, IBS can be disabling. They may be unable to work, attend social events, or even travel short distances.

Patients are considered to have chronic constipation if they have fewer than three complete spontaneous bowel movements per week and at least one of the following symptoms for at least 25 percent of those bowel movements: straining, hard stools, incomplete evacuation.

Physicians with IBS-C or CIC patients who meet the IND criteria should contact Novartis at 888- 669-6682 or 866-248-1348. Those who do not qualify for the Zelnorm treatment protocol may contact FDA’s Division for Drug Information about other options at 888-463-6332.

FDA Announces Program to Enhance States’ Food Safety Programs
Goal is to Strengthen Safety of Food Facilities Overseen by States

The U.S. Food and Drug Administration today launched a national program to bring about the adoption of more uniform, equivalent, and high quality regulatory programs by state agencies responsible for regulating facilities that manufacture, process, pack, or hold food under FDA’s jurisdiction.

“This risk-based program represents a significant step in further integrating our food safety system,” said Margaret O’K. Glavin, FDA’s associate commissioner for regulatory affairs. “We realize it will be several years before it’s fully implemented, but we’re confident this program will bring great benefits to the public health.”

Currently, programmatic activities can vary from state to state and such variations can lead to inconsistencies in oversight of food safety. Adoption of voluntary standards for state regulatory programs will establish a uniform basis for measuring and improving the performance of state programs for regulating manufactured food and help the state and federal authorities reduce foodborne illness hazards in food facilities.

The Manufactured Food Regulatory Program Standards are the result of five years of intensive cooperative effort by federal and state regulators. The standards define best practices for the critical elements of state regulatory programs designed to protect the public from foodborne illness and injury, including:

the program’s regulatory foundation;
staff training;
inspection;
quality assurance;
food defense preparedness and response;
foodborne illness and incident investigation;
enforcement;
education and outreach;
resource management;
laboratory resources; and
program assessment.
Each standard has corresponding self-assessment worksheets. Several standards have supplemental worksheets and forms to assist state regulators in determining whether their state program addresses all of the elements in the standards.

The Manufactured Food Regulatory Program Standards have been approved by the U.S. Office of Management and Budget and will be pilot-tested in New York, Oregon, and Missouri before September 30, 2007.

FDA regulates about 80 percent of the food supply, which includes food for humans and animals, except meat products, poultry products, and egg products, which are regulated by the U.S. Department of Agriculture.

Data from the U.S. Military Health System will soon help the U.S. Food and Drug Administration make decisions affecting the safety and use of FDA-regulated products for all Americans.

The FDA, part of the U.S. Department of Health and Human Services, and the Department of Defense today announced a partnership to share data and expertise related to the review and use of FDA-regulated drugs, biologics, and medical devices.

General patient data such as prescriptions, lab results and patient weight will be used by the FDA to spot trends, which may identify potential concerns as well as recognize benefits of products.

The two agencies will protect all personal health information exchanged under the agreement, in accordance with federal law.

"FDA is privileged to collaborate with DoD to protect the health of all Americans," said Commissioner of Food and Drugs Andrew C. von Eschenbach, M.D. "The opportunity to create systems to monitor the safety of products should directly benefit those cared for by the armed services as well as many others."

The partnership, which will operate under a memorandum of understanding (MOU), is part of the FDA's Sentinel Network, a medical product safety initiative first announced in January 2007. This initiative is intended to explore linking private sector and public sector information to create a virtual, integrated, electronic network. The MOU was signed by von Eschenbach and Assistant Secretary of Defense for Health Affairs S. Ward Casscells, M.D. Among the DoD programs involved in the agreement is TRICARE, the agency that administers the health care plan serving 9.1 million members of the uniformed services, retirees and their families. The first data shared will most likely be TRICARE prescription information.

"Currently, most drug studies performed prior to FDA approval involve about 1,000 patients, and follow up studies use similar numbers," said Casscells. "Data from the Military Health System will expand the possibilities to include millions of patients when it comes to follow up research. We have more than 6.6 million beneficiaries using the TRICARE pharmacy benefit alone."

The DoD and FDA will meet later this year to establish specific procedures and safeguards necessary to implement the MOU. Long range plans for the Sentinel Network call for a seamless national electronic information network that will include everything from new medical product information and patient care records to adverse event reports, and domestic and foreign clinical trials.

For more information:
FDA-DoD Memorandum of Understanding
http://www.fda.gov/oc/mous/domestic/FDA-DOD-INFO.html

FDA Warns of Potential Botulism Risk from Canned French Cut Green Beans
Product Marketed Under a Variety of Brand Names
The U.S. Food and Drug Administration (FDA) is warning consumers not to eat certain brands of French Cut Green Beans in 14.5 ounce cans manufactured by Lakeside Foods Inc, of Manitowoc, Wisconsin because the product may not have been processed adequately to eliminate the potential for botulism toxin. This warning is not related to another recent warning for botulism.

The canned green beans may cause botulism if consumed. FDA is providing this warning to make consumers aware of the possible risk of serious illness from eating these products. As of August 1, 2007, FDA had not received reports of illnesses related to the product.

The botulism toxin is very potent, and botulism is a life-threatening illness. Symptoms of botulism can begin from six hours to two weeks after eating food that contains the toxin. The symptoms may include double vision, blurred vision, drooping eyelids, slurred speech, difficulty swallowing, dry mouth, 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 also may cause paralysis of the breathing muscles, which can result in death unless assistance with breathing (mechanical ventilation) is provided. Individuals who show these symptoms and who may have recently eaten the product should seek immediate medical attention.

The affected Lakeside cut green beans are sold nationwide under the following labels: Albertson's, Happy Harvest, Best Choice, Food Club, Bogopa, Valu Time, Hill Country Fare, HEB, Laura Lynn, Kroger, No Name, North Pride, Shop N Save, Shoppers Valu, Schnucks, Cub Foods, Dierbergs, Flavorite, IGA, Best Choice and Thrifty Maid. The specific codes (top line of can code) involved are: EAA5247, EAA5257, EAA5267, EAA5277, EAB5247, EAB5257, ECA5207, ECA5217, ECA5227, ECA5297, ECB5207, ECB5217, ECB5227, ECB5307.

Consumers who have any of these products or any foods made with these products should dispose of them immediately. If the code on an affected can is missing or unreadable, consumers should throw the product out.

Lakeside Foods has informed FDA that it is voluntarily recalling all of the potentially contaminated products.

Lakeside Foods recommends that consumers with any questions or concerns about the recall should call the company at 800-466-3834 ext. 4090.

The U.S. Food and Drug Administration (FDA) today approved maraviroc, an antiretroviral drug for use in adult HIV patients. Maraviroc, sold under the trade name Selzentry, is the first in a new class of drugs designed to slow the advancement of HIV and received priority review by the FDA.

Maraviroc is approved for use in combination with other antiretroviral drugs for the treatment of adults with CCR5-tropic HIV-1, who have been treated with other HIV medications and who have evidence of elevated levels of HIV in their blood (viral load). Rather than fighting HIV inside white blood cells, maraviroc prevents the virus from entering uninfected cells by blocking the predominant route of entry, the CCR5 co-receptor. CCR5 is a protein on the surface of some types of immune cells. Among patients who have previously received HIV medications, approximately 50 percent to 60 percent have circulating CCR5-tropic HIV-1. "This is an important new product for many HIV-infected patients who have not responded to other treatments and have few options," said Steven Galson, M.D., M.P.H., director of FDA's Center for Drug Evaluation and Research.

The product label includes a boxed warning about liver toxicity (hepatoxicity) and a statement in the Warnings/Precautions section about the possibility of heart attacks. The FDA's approval of maraviroc is based on safety and effectiveness data from two double-blind, placebo-controlled studies. The 1,076 clinical trial participants were selected because they still showed evidence of HIV-1 in their blood, despite treatment with other HIV medications. A blood test for CCR5 tropic HIV-1 was used during clinical trials to identify patients appropriate for

The safety and effectiveness of maraviroc have not been established in adult and pediatric patients who have never been treated with any other HIV drug. Additionally, the drug has not been tested or studied in pregnant women. The FDA recommends that HIV positive women should not breast feed, whether or not they are on antiretroviral medications.

The most common adverse events reported with maraviroc were cough, fever, upper respiratory tract infections, rash, musculoskeletal symptoms, abdominal pain, and dizziness.

Maraviroc is distributed by New York-based Pfizer Inc.

FDA Warns Consumers to Avoid Red Yeast Rice Products Promoted on Internet as Treatments for High Cholesterol
Products found to contain unauthorized drug
The U.S. Food and Drug Administration is warning consumers not to buy or eat three red yeast rice products promoted and sold on Web sites. The products may contain an unauthorized drug that could be harmful to health. The products are promoted as dietary supplements for treating high cholesterol.

The potentially harmful products are: Red Yeast Rice and Red Yeast Rice/Policosonal Complex, sold by Swanson Healthcare Products, Inc. and manufactured by Nature’s Value Inc. and Kabco Inc., respectively; and Cholestrix, sold by Sunburst Biorganics. FDA testing revealed the products contain lovastatin, the active pharmaceutical ingredient in Mevacor, a prescription drug approved for marketing in the United States as a treatment for high cholesterol.

“This risk is even more serious because consumers may not know the side effects associated with lovastatin and the fact that it can adversely interact with other medications," said Steven Galson, M.D., M.P.H., director of FDA's Center for Drug Evaluation and Research.

These red yeast rice products are a threat to health because the possibility exists that lovastatin can cause severe muscle problems leading to kidney impairment. This risk is greater in patients who take higher doses of lovastatin or who take lovastatin and other medicines that increase the risk of muscle adverse reactions. These medicines include the antidepressant nefazodone, certain antibiotics, drugs used to treat fungal infections and HIV infections, and other cholesterol-lowering medications.

FDA has issued warning letters advising Swanson and Sunburst Biorganics to stop promoting and selling the products. Companies that do not resolve violations in FDA warning letters risk enforcement actions, such as an injunction against continuing violations and a seizure of illegal products.

The FDA warning letters state that the products Red Yeast Rice, Red Yeast Rice/Policosonal Complex, and Cholestrix, sold on the firm’s websites, are unapproved new drugs that are marketed in violation of the Federal Food, Drug, and Cosmetic Act. The warning letters are available on FDA’s Web site: www.accessdata.fda.gov/scripts/wlcfm/recentfiles.cfm.

FDA advises consumers who use any red yeast rice product to consult their health care provider if they experience problems that may be due to the product.

Report adverse events related to these products to MedWatch, the FDA’s voluntary reporting program:
www.fda.gov/medwatch/report.htm; 800-332-1088; Fax: 800-332-0178; and MedWatch, Food and Drug Administration, 5600 Fishers Lane, Rockville, MD, 20852-9787.

FDA Takes Action Against Iowa Dairy for Illegal Drug Residues Found in Cows
A Complaint and Consent Decree of Permanent Injunction were filed Wednesday, August 8 in the U.S. District Court for the Northern District of Iowa, Western Division, against Ysselstein Dairy Inc., Rock Valley, Iowa, and its owner and president, Sjerp W. Ysselstein, after illegal drug residues were found in the dairy's cows. The permanent injunction will not become effective against Ysselstein Dairy until the Court signs and enters the Consent Decree. The action follows FDA investigations into the dairy and its practices.

The FDA is concerned about the sale of animals for human food that may contain illegal levels of animal drugs because of the potential for adverse effects on human health. The FDA approves new animal drugs with requirements, including a specified time period to withdraw an animal from treatment prior to slaughter, to assure that a drug has been depleted from edible tissue to a level safe for humans.

Ysselstein Dairy produces milk for human consumption and sells dairy cows for slaughter for human consumption. The injunction is based on nine illegal residues in the edible tissue of seven dairy cows sampled by the U.S. Department of Agriculture's Food Safety Inspection Service (FSIS) between July 21, 1992, and March 10, 2006. The drug residues found by FSIS included antibiotics such as tetracycline, sulfadimethoxine, flunixin, oxytetracycline, and penicillin at levels not permitted by the FDA.

Under the terms of the Consent Decree, the dairy and Ysselstein must implement systems for identifying animals, keeping records, drug control, drug accountability, and drug residue withdrawal control. Furthermore, if the FDA informs the defendants of their not being in compliance with the terms of the Decree or the Federal Food, Drug, and Cosmetic Act, the FDA may require them to cease operations until they are in compliance. The Decree also provides for the dairy and Ysselstein to pay a fine for each day they fail to comply with the Decree and for each animal that they sell or deliver for sale in violation of the Decree.

FDA's Kansas City District Office conducted the investigations that led to the Consent Decree. FDA's Center for Veterinary Medicine Division of Compliance, FDA's Office of the Chief Counsel, and the U.S. Attorney's Office in the Northern District of Iowa processed and filed the case.

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