NEXAVAR APPROVED BY FDA TO TREAT LATE-STAGE DIFFERENTIATED THYROID CANCER

FROM:  U.S. FOOD AND DRUG ADMINISTRATION 
FDA NEWS RELEASE
 For Immediate Release: Nov. 22, 2013

FDA approves Nexavar to treat type of thyroid cancer

The U.S. Food and Drug Administration today expanded the approved uses of Nexavar (sorafenib) to treat late-stage (metastatic) differentiated thyroid cancer.

Thyroid cancer is a cancerous growth of the thyroid gland, which is located in the neck. Differentiated thyroid cancer is the most common type of thyroid cancer. The National Cancer Institute estimates that 60,220 Americans will be diagnosed with thyroid cancer and 1,850 will die from the disease in 2013.

Nexavar works by inhibiting multiple proteins in cancer cells, limiting cancer cell growth and division. The drug’s new use is intended for patients with locally recurrent or metastatic, progressive differentiated thyroid cancer that no longer responds to radioactive iodine treatment.

“Differentiated thyroid cancer can be challenging to treat, especially when unresponsive to conventional therapies,” said Richard Pazdur, M.D., director of the Office of Hematology and Oncology Products in the FDA’s Center for Drug Evaluation and Research. “Today’s approval demonstrates the FDA’s commitment to expediting the availability of treatment options for patients with difficult-to-treat diseases.”

The safety and effectiveness of Nexavar were established in a clinical study involving 417 participants with locally recurrent or metastatic, progressive differentiated thyroid cancer that does not respond to radioactive iodine treatment. Nexavar increased the length of time patients lived without the cancer progressing (progression-free survival) by 41 percent. Half of patients receiving Nexavar lived without cancer progression for at least 10.8 months compared to at least 5.8 months for participants receiving a placebo.

The most common side effects in patients treated with Nexavar were diarrhea, fatigue, infection, hair loss (alopecia), hand-foot skin reaction, rash, weight loss, decreased appetite, nausea, gastrointestinal and abdominal pains and high blood pressure (hypertension). Thyroid stimulating hormone, a potential promoter of thyroid cancer, is more likely to become elevated while on treatment with Nexavar, requiring adjustment of thyroid hormone replacement therapy.

The FDA completed its review of Nexavar’s new indication under its priority review program. This program provides for an expedited, six-month review for drugs that may offer a significant improvement in safety or effectiveness of the treatment, prevention or diagnosis of a serious condition. Nexavar also received orphan-product designation by the FDA because it is intended to treat a rare disease or condition.

The FDA approved Nexavar to treat advanced kidney cancer in 2005. In 2007, the agency expanded the drug’s label to treat liver cancer that cannot be surgically removed.

Nexavar is co-marketed by Bayer HealthCare Pharmaceuticals Inc., based in Wayne, N.J., and Onyx Pharmaceuticals, based in South San Francisco, Calif.

For more information:

FDA: Office of Hematology and Oncology Products

FDA: Approved Drugs: Questions and Answers

NCI: Thyroid Cancer

The FDA, an agency within the U.S. Department of Health and Human Services, promotes and protects the public health by, among other things, assuring the safety, effectiveness, and security of human and veterinary drugs, vaccines and other biological products for human use, and medical devices. The agency also is responsible for the safety and security of our nation’s food supply, cosmetics, dietary supplements, products that give off electronic radiation, and for regulating tobacco products.

Consumer Inquiries: 888-INFO-FDA

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Editor's Note: This release has been updated to include Onyx Pharmaceuticals as a co-marketer of the product.

FDA TELLS PEOPLE TO CUT DOWN ON ACRYLAMIDE', OFFERS WAYS TO CUT BACK ON CONSUMPTION

FROM:  U.S. FOOD AND DRUG ADMINISTRATION 
You Can Help Cut Acrylamide in Your Diet

If you're trying to lose weight, you may already be telling your waiter to hold the fries. Now there's another health benefit you can reap: Cutting down on certain fried foods can also help you cut down on the amount of acrylamide you eat. That's a good thing because high levels of acrylamide have been found to cause cancer in animals, and on that basis scientists believe it is likely to cause cancer in humans as well.

FDA chemist Lauren Robin explains that acrylamide is a chemical that can form in some foods—mainly plant-based foods—during high-temperature cooking processes like frying and baking. These include potatoes, cereals, coffee, crackers or breads, dried fruits and many other foods. According to the Grocery Manufacturers Association, acrylamide is found in 40 percent of the calories consumed in the average American diet.

While acrylamide has probably been around as long as people have been baking, roasting, toasting or frying foods, it was only in 2002 that scientists first discovered the chemical in food. Since then, the FDA has been actively investigating the effects of acrylamide as well as potential measures to reduce it. Today, the FDA posts a draft document with practical strategies to help growers, manufacturers and food service operators lower the amount of acrylamide in foods associated with higher levels of the chemical.

In addition, there are a number of steps you and your family can take to cut down on the amount of acrylamide in the foods you eat.

Acrylamide forms from sugars and an amino acid that are naturally present in food. It does not form, or forms at lower levels, in dairy, meat and fish products. The formation occurs when foods are cooked at home and in restaurants as well as when they are made commercially.

"Generally speaking, acrylamide is more likely to accumulate when cooking is done for longer periods or at higher temperatures," Robin says. Boiling and steaming foods do not typically form acrylamide.
Tips for Cutting Down on Acrylamide
Given the widespread presence of acrylamide in foods, it isn't feasible to completely eliminate acrylamide from one's diet, Robin says. Nor is it necessary. Removing any one or two foods from your diet would not have a significant effect on overall exposure to acrylamide.

However, here are some steps you can take to help decrease the amount of acrylamide that you and your family consume:

Frying causes acrylamide formation. If frying frozen fries, follow manufacturers' recommendations on time and temperature and avoid overcooking, heavy crisping or burning.
Toast bread to a light brown color rather than a dark brown color. Avoid very brown areas.
Cook cut potato products such as frozen french fries to a golden yellow color rather than a brown color. Brown areas tend to contain more acrylamide.
Do not store potatoes in the refrigerator, which can increase acrylamide during cooking. Keep potatoes outside the refrigerator in a dark, cool place, such as a closet or a pantry.
FDA also recommends that you adopt a healthy eating plan, consistent with the Dietary Guidelines for Americans, including:

Eat plenty of fruits, vegetables, whole grains, and fat-free or low-fat milk products.
Include lean meats, poultry, fish, beans, eggs and nuts.
Choose foods low in saturated fats, trans fat (which both raises your bad LDL cholesterol and lowers your good HDL cholesterol and is linked to heart attacks), cholesterol, salt and added sugars.
This article appears on FDA's Consumer Updates page, which features the latest on all FDA-regulated products.

November 14, 2013

FDA APPROVES DRUG TO TREAT AGGRESSIVE TYPE OF BLOOD CANCER

FROM:  U.S. FOOD AND DRUG ADMINISTRATION 
FDA approves Imbruvica for rare blood cancer
Second drug with breakthrough therapy designation to receive FDA approval

The U.S. Food and Drug Administration today approved Imbruvica (ibrutinib) to treat patients with mantle cell lymphoma (MCL), a rare and aggressive type of blood cancer.

MCL is a rare form of non-Hodgkin lymphoma and represents about 6 percent of all non-Hodgkin lymphoma cases in the United States. By the time MCL is diagnosed, it usually has already spread to the lymph nodes, bone marrow and other organs.

Imbruvica is intended for patients with MCL who have received at least one prior therapy. It works by inhibiting the enzyme needed by the cancer to multiply and spread. Imbruvica is the third drug approved to treat MCL. Velcade (2006) and Revlimid (2013) are also approved to treat the disease.

“Imbruvica’s approval demonstrates the FDA’s commitment to making treatments available to patients with rare diseases,” said Richard Pazdur, M.D., director of the Office of Hematology and Oncology Products in the FDA’s Center for Drug Evaluation and Research. “The agency worked cooperatively with the companies to expedite the drug’s development, review and approval, reflecting the promise of the Breakthrough Therapy Designation program.”

Imbruvica is the second drug with breakthrough therapy designation to receive FDA approval. The Food and Drug Administration Safety and Innovation Act, passed in July 2012, gave the FDA the ability to designate a drug a breakthrough therapy at the request of the sponsor if preliminary clinical evidence indicates the drug may offer a substantial improvement over available therapies for patients with serious or life-threatening diseases.

The FDA is approving Imbruvica under the agency's accelerated approval program, which allows the FDA to approve a drug to treat a serious disease based on clinical data showing that the drug has an effect on a surrogate endpoint that is reasonably likely to predict a clinical benefit to patients. This program provides earlier patient access to promising new drugs while the company conducts confirmatory clinical trials. The FDA also granted Imbruvica priority review and orphan-product designation because the drug demonstrated the potential to be a significant improvement in safety or effectiveness in the treatment of a serious condition and is intended to treat a rare disease, respectively.

Imbruvica’s accelerated approval for MCL is based on a study where 111 participants were given Imbruvica daily until their disease progressed or side effects became intolerable. Results showed nearly 66 percent of participants had their cancer shrink or disappear after treatment (overall response rate). An improvement in survival or disease-related symptoms has not been established.

The most common side effects reported in participants receiving Imbruvica are low levels of platelets in the blood (thrombocytopenia), diarrhea, a decrease in infection-fighting white blood cells (neutropenia), anemia, fatigue, musculoskeletal pain, swelling (edema), upper respiratory infection, nausea, bruising, shortness of breath (dyspnea), constipation, rash, abdominal pain, vomiting, and decreased appetite. Other clinically significant side effects include bleeding, infections, kidney problems and the development of other types of cancers.

Imbruvica is co-marketed by Sunnyvale, Calif.-based Pharmacyclics and Raritan, N.J.-based Janssen Biotech, Inc. Velcade (bortezomib) is marketed by Millennium Pharmaceuticals, based in Cambridge, Mass. Revlimid (lenalidomide) is marketed by Summit, N.J.-based Celgene.

FDA WARNS OF RISKS TO PETS TAKING PAIN MEDICATION

FROM:  U.S. FOOD AND DRUG ADMINISTRATION 
Pain Medicines for Pets: Know the Risks

Your 9-year-old German Shepherd is limping, and you think that arthritis may be setting in. A trip to the veterinarian proves that you’re right—it’s osteoarthritis, a degeneration of the cartilage and bone that affects joints. The veterinarian prescribes a non-steroidal anti-inflammatory drug (NSAID).

NSAIDs are a class of drugs extensively used in both human and veterinary medicine for their anti-fever, anti-inflammatory and pain-relieving properties, and they are the most commonly prescribed pain relievers for animals. Inflammation—the body’s response to irritation or injury—is characterized by redness, warmth, swelling, and pain. NSAIDs work by blocking the production of chemicals produced by the body that play a role in inflammation.

“Scientists consider NSAIDs the cornerstone of osteoarthritis therapy in dogs,” says Melanie McLean, D.V.M., a veterinarian at the Food and Drug Administration (FDA). Some NSAIDS are also used to manage pain after surgery in both dogs and cats. No NSAID has been approved for long-term use in cats.

NSAIDs carry risks as well as benefits, however, and all dogs and cats should undergo a thorough physical examination by a veterinarian—including a discussion of the pet’s medical history— before beginning NSAID therapy. McLean notes that it’s also important that you talk to your veterinarian about possible side effects, including those that could signal danger.

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Risks and Side Effects
NSAIDS are associated with gastrointestinal ulcers/perforations, kidney, and liver toxicity (damage done by exposure to medications or chemicals) and must be used cautiously in animals with pre-existing kidney or liver problems.

Because most liver-associated toxicities occur during the first three weeks, it’s especially important to closely monitor the results of blood tests during the early stages of long-term NSAID treatment in dogs. Also, before starting long-term treatment with NSAIDs in dogs, blood tests should be conducted to establish baseline data and then repeated on a regular basis. McLean recommends that you talk with your veterinarian about how often this blood work should be done.

Some of the most common side effects of NSAIDS in animals reported to FDA are:

vomiting
decreased to no appetite
decreased activity level
diarrhea
While your animal is taking NSAIDs, continuously monitor the pet for these side effects as well as looking for blood in the feces, tar-like stools, yellowing of the whites of the eyes, or yellowing of the gums. If you see these, call your veterinarian immediately, McLean says. Other reported side effects include stomach and intestinal ulcers, intestinal perforation (a hole in the wall of the intestine), kidney failure, liver failure and death.

Giving two NSAIDs at the same time, or giving an NSAID with a steroid, such as prednisone, can significantly increase the risk and severity of side effects, especially gastrointestinal toxicity.

Risks associated with NSAIDs are detailed on the package inserts and the client information sheets that accompany all FDA-approved veterinary oral NSAIDs.

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Are OTC Meds for People Safe for Pets?
McLean says that it’s not unusual for pet owners to want to give their animals NSAIDs or acetaminophen (Tylenol and other brands, which are not NSAIDs) straight from their own medicine cabinets. “Many people don’t realize that a medicine that’s safe for people may not be safe for dogs or cats, or that a dose that is safe for people may not be safe for their pets,” she notes.

In fact, some over-the-counter (OTC) human pain relievers can be toxic, or even deadly, in pets. McLean suggests that you check with your veterinarian first if you want to give your animal OTC human drugs.

“You should always check with your veterinarian first before giving your animal any kind of medication, prescription or over-the-counter,” she notes. Similarly, pet owners should not assume that a medicine that is safe for one animal is necessarily safe for another.

Communication with your veterinarian is essential. Before giving your animal an NSAID:

Make sure you know what the medication is being prescribed for, how much to give and how long to give it.
Discuss possible side effects and symptoms, especially those that require an immediate call to the vet.
Tell your veterinarian if the pet has a history of gastrointestinal problems, such as stomach ulcers, or surgery on the stomach or intestines.
Tell your veterinarian if your pet is on any other medications or supplements.
This article appears on FDA's Consumer Updates page, which features the latest on all FDA-regulated products.

JOHNSON & JOHNSON TO PAY OVER $2.2 BILLION TO RESOLVE ALLEGATIONS RELATED TO DOCTOR KICKBACK SCHEME

FROM:  U.S. JUSTICE DEPARTMENT 
Monday, November 4, 2013
Johnson & Johnson to Pay More Than $2.2 Billion to Resolve Criminal and Civil Investigations
Allegations Include Off-label Marketing and Kickbacks to Doctors and Pharmacists

WASHINGTON - Global health care giant Johnson & Johnson (J&J) and its subsidiaries will pay more than $2.2 billion to resolve criminal and civil liability arising from allegations relating to the prescription drugs Risperdal, Invega and Natrecor, including promotion for uses not approved as safe and effective by the Food and Drug Administration (FDA) and payment of kickbacks to physicians and to the nation’s largest long-term care pharmacy provider.  The global resolution is one of the largest health care fraud settlements in U.S. history, including criminal fines and forfeiture totaling $485 million and civil settlements with the federal government and states totaling $1.72 billion.


“The conduct at issue in this case jeopardized the health and safety of patients and damaged the public trust,” said Attorney General Eric Holder.  “This multibillion-dollar resolution demonstrates the Justice Department’s firm commitment to preventing and combating all forms of health care fraud.  And it proves our determination to hold accountable any corporation that breaks the law and enriches its bottom line at the expense of the American people.”


The resolution includes criminal fines and forfeiture for violations of the law and civil settlements based on the False Claims Act arising out of multiple investigations of the company and its subsidiaries.


“When companies put profit over patients’ health and misuse taxpayer dollars, we demand accountability,” said Associate Attorney General Tony West.  “In addition to significant monetary sanctions, we will ensure that non-monetary measures are in place to facilitate change in corporate behavior and help ensure the playing field is level for all market participants.”


In addition to imposing substantial monetary sanctions, the resolution will subject J&J to stringent requirements under a Corporate Integrity Agreement (CIA) with the Department of Health and Human Services Office of Inspector General (HHS-OIG).  This agreement is designed to increase accountability and transparency and prevent future fraud and abuse.


“As patients and consumers, we have a right to rely upon the claims drug companies make about their products,” said Assistant Attorney General for the Justice Department’s Civil Division Stuart F. Delery.  “And, as taxpayers, we have a right to ensure that federal health care dollars are spent appropriately.  That is why this Administration has continued to pursue aggressively – with all of our available law enforcement tools -- those companies that corrupt our health care system.”


J&J Subsidiary Janssen Pleads Guilty to Misbranding Antipsychotic Drug


In a criminal information filed today in the Eastern District of Pennsylvania, the government charged that, from March 3, 2002, through Dec. 31, 2003, Janssen Pharmaceuticals Inc., a J&J subsidiary, introduced the antipsychotic drug Risperdal into interstate commerce for an unapproved use, rendering the product misbranded.  For most of this time period, Risperdal was approved only to treat schizophrenia.  The information alleges that Janssen’s sales representatives promoted Risperdal to physicians and other prescribers who treated elderly dementia patients by urging the prescribers to use Risperdal to treat symptoms such as anxiety, agitation, depression, hostility and confusion.  The information alleges that the company created written sales aids for use by Janssen’s ElderCare sales force that emphasized symptoms and minimized any mention of the FDA-approved use, treatment of schizophrenia.  The company also provided incentives for off-label promotion and intended use by basing sales representatives’ bonuses on total sales of Risperdal in their sales areas, not just sales for FDA-approved uses.


In a plea agreement resolving these charges, Janssen admitted that it promoted Risperdal to health care providers for treatment of psychotic symptoms and associated behavioral disturbances exhibited by elderly, non-schizophrenic dementia patients.  Under the terms of the plea agreement, Janssen will pay a total of $400 million, including a criminal fine of $334 million and forfeiture of $66 million.  Janssen’s guilty plea will not be final until accepted by the U.S. District Court.

The Federal Food, Drug, and Cosmetic Act (FDCA) protects the health and safety of the public by ensuring, among other things, that drugs intended for use in humans are safe and effective for their intended uses and that the labeling of such drugs bear true, complete and accurate information.  Under the FDCA, a pharmaceutical company must specify the intended uses of a drug in its new drug application to the FDA.  Before approval, the FDA must determine that the drug is safe and effective for those specified uses.  Once the drug is approved, if the company intends a different use and then introduces the drug into interstate commerce for that new, unapproved use, the drug becomes misbranded.  The unapproved use is also known as an “off-label” use because it is not included in the drug’s FDA-approved labeling.

“When pharmaceutical companies interfere with the FDA’s mission of ensuring that drugs are safe and effective for the American public, they undermine the doctor-patient relationship and put the health and safety of patients at risk,” said Director of the FDA’s Office of Criminal Investigations John Roth.  “Today’s settlement demonstrates the government’s continued focus on pharmaceutical companies that put profits ahead of the public’s health.  The FDA will continue to devote resources to criminal investigations targeting pharmaceutical companies that disregard the drug approval process and recklessly promote drugs for uses that have not been proven to be safe and effective.”

J&J and Janssen Settle Civil Allegations of Targeting Vulnerable Patients  with the Drugs Risperdal and Invega for Off-Label Uses

In a related civil complaint filed today in the Eastern District of Pennsylvania, the United States alleges that Janssen marketed Risperdal to control the behaviors and conduct of the nation’s most vulnerable patients: elderly nursing home residents, children and individuals with mental disabilities.  The government alleges that J&J and Janssen caused false claims to be submitted to federal health care programs by promoting Risperdal for off-label uses that federal health care programs did not cover, making false and misleading statements about the safety and efficacy of Risperdal and paying kickbacks to physicians to prescribe Risperdal.

“J&J’s promotion of Risperdal for unapproved uses threatened the most vulnerable populations of our society – children, the elderly and those with developmental disabilities,” said U.S. Attorney for the Eastern District of Pennsylvania Zane Memeger.  “This historic settlement sends the message that drug manufacturers who place profits over patient care will face severe criminal and civil penalties.”

In its complaint, the government alleges that the FDA repeatedly advised Janssen that marketing Risperdal as safe and effective for the elderly would be “misleading.”  The FDA cautioned Janssen that behavioral disturbances in elderly dementia patients were not necessarily manifestations of psychotic disorders and might even be “appropriate responses to the deplorable conditions under which some demented patients are housed, thus raising an ethical question regarding the use of an antipsychotic medication for inappropriate behavioral control.”

The complaint further alleges that J&J and Janssen were aware that Risperdal posed serious health risks for the elderly, including an increased risk of strokes, but that the companies downplayed these risks.  For example, when a J&J study of Risperdal showed a significant risk of strokes and other adverse events in elderly dementia patients, the complaint alleges that Janssen combined the study data with other studies to make it appear that there was a lower overall risk of adverse events.  A year after J&J had received the results of a second study confirming the increased safety risk for elderly patients taking Risperdal, but had not published the data, one physician who worked on the study cautioned Janssen that “[a]t this point, so long after [the study] has been completed … we must be concerned that this gives the strong appearance that Janssen is purposely withholding the findings.”

The complaint also alleges that Janssen knew that patients taking Risperdal had an increased risk of developing diabetes, but nonetheless promoted Risperdal as “uncompromised by safety concerns (does not cause diabetes).”  When Janssen received the initial results of studies indicating that Risperdal posed the same diabetes risk as other antipsychotics, the complaint alleges that the company retained outside consultants to re-analyze the study results and ultimately published articles stating that Risperdal was actually associated with a lower risk of developing diabetes.

The complaint alleges that, despite the FDA warnings and increased health risks, from 1999 through 2005, Janssen aggressively marketed Risperdal to control behavioral disturbances in dementia patients through an “ElderCare sales force” designed to target nursing homes and doctors who treated the elderly.  In business plans, Janssen’s goal was to “[m]aximize and grow RISPERDAL’s market leadership in geriatrics and long term care.”  The company touted Risperdal as having “proven efficacy” and “an excellent safety and tolerability profile” in geriatric patients.

In addition to promoting Risperdal for elderly dementia patients, from 1999 through 2005, Janssen allegedly promoted the antipsychotic drug for use in children and individuals with mental disabilities.  The complaint alleges that J&J and Janssen knew that Risperdal posed certain health risks to children, including the risk of elevated levels of prolactin, a hormone that can stimulate breast development and milk production.  Nonetheless, one of Janssen’s Key Base Business Goals was to grow and protect the drug’s market share with child/adolescent patients.  Janssen instructed its sales representatives to call on child psychiatrists, as well as mental health facilities that primarily treated children, and to market Risperdal as safe and effective for symptoms of various childhood disorders, such as attention deficit hyperactivity disorder, oppositional defiant disorder, obsessive-compulsive disorder and autism.  Until late 2006, Risperdal was not approved for use in children for any purpose, and the FDA repeatedly warned the company against promoting it for use in children.

The government’s complaint also contains allegations that Janssen paid speaker fees to doctors to influence them to write prescriptions for Risperdal.  Sales representatives allegedly told these doctors that if they wanted to receive payments for speaking, they needed to increase their Risperdal prescriptions.

In addition to allegations relating to Risperdal, today’s settlement also resolves allegations relating to Invega, a newer antipsychotic drug also sold by Janssen.  Although Invega was approved only for the treatment of schizophrenia and schizoaffective disorder, the government alleges that, from 2006 through 2009, J&J and Janssen marketed the drug for off-label indications and made false and misleading statements about its safety and efficacy.

As part of the global resolution, J&J and Janssen have agreed to pay a total of $1.391 billion to resolve the false claims allegedly resulting from their off-label marketing and kickbacks for Risperdal and Invega.  This total includes $1.273 billion to be paid as part of the resolution announced today, as well as $118 million that J&J and Janssen paid to the state of Texas in March 2012 to resolve similar allegations relating to Risperdal.  Because Medicaid is a joint federal-state program, J&J’s conduct caused losses to both the federal and state governments.  The additional payment made by J&J as part of today’s settlement will be shared between the federal and state governments, with the federal government recovering $749 million, and the states recovering $524 million.  The federal government and Texas each received $59 million from the Texas settlement.

Kickbacks to Nursing Home Pharmacies

The civil settlement also resolves allegations that, in furtherance of their efforts to target elderly dementia patients in nursing homes, J&J and Janssen paid kickbacks to Omnicare Inc., the nation’s largest pharmacy specializing in dispensing drugs to nursing home patients.  In a complaint filed in the District of Massachusetts in January 2010, the United States alleged that J&J paid millions of dollars in kickbacks to Omnicare under the guise of market share rebate payments, data-purchase agreements, “grants” and “educational funding.”  These kickbacks were intended to induce Omnicare and its hundreds of consultant pharmacists to engage in “active intervention programs” to promote the use of Risperdal and other J&J drugs in nursing homes.  Omnicare’s consultant pharmacists regularly reviewed nursing home patients’ medical charts and made recommendations to physicians on what drugs should be prescribed for those patients.  Although consultant pharmacists purported to provide “independent” recommendations based on their clinical judgment, J&J viewed the pharmacists as an “extension of [J&J’s] sales force.”

J&J and Janssen have agreed to pay $149 million to resolve the government’s contention that these kickbacks caused Omnicare to submit false claims to federal health care programs.  The federal share of this settlement is $132 million, and the five participating states’ total share is $17 million.  In 2009, Omnicare paid $98 million to resolve its civil liability for claims that it accepted kickbacks from J&J and Janssen, along with certain other conduct.

“Consultant pharmacists can play an important role in protecting nursing home residents from the use of antipsychotic drugs as chemical restraints,” said U.S. Attorney for the District of Massachusetts Carmen Ortiz.  “This settlement is a reminder that the recommendations of consultant pharmacists should be based on their independent clinical judgment and should not be the product of money paid by drug companies.”

Off-Label Promotion of the Heart Failure Drug Natrecor

The civil settlement announced today also resolves allegations that J&J and another of its subsidiaries, Scios Inc., caused false and fraudulent claims to be submitted to federal health care programs for the heart failure drug Natrecor.  In August 2001, the FDA approved Natrecor to treat patients with acutely decompensated congestive heart failure who have shortness of breath at rest or with minimal activity.  This approval was based on a study involving hospitalized patients experiencing severe heart failure who received infusions of Natrecor over an average 36-hour period.

In a civil complaint filed in 2009 in the Northern District of California, the government alleged that, shortly after Natrecor was approved, Scios launched an aggressive campaign to market the drug for scheduled, serial outpatient infusions for patients with less severe heart failure – a use not included in the FDA-approved label and not covered by federal health care programs.  These infusions generally involved visits to an outpatient clinic or doctor’s office for four- to six-hour infusions one or two times per week for several weeks or months.

The government’s complaint alleged that Scios had no sound scientific evidence supporting the medical necessity of these outpatient infusions and misleadingly used a small pilot study to encourage the serial outpatient use of the drug.  Among other things, Scios sponsored an extensive speaker program through which doctors were paid to tout the purported benefits of serial outpatient use of Natrecor.  Scios also urged doctors and hospitals to set up outpatient clinics specifically to administer the serial outpatient infusions, in some cases providing funds to defray the costs of setting up the clinics, and supplied providers with extensive resources and support for billing Medicare for the outpatient infusions.

As part of today’s resolution, J&J and Scios have agreed to pay the federal government $184 million to resolve their civil liability for the alleged false claims to federal health care programs resulting from their off-label marketing of Natrecor.  In October 2011, Scios pleaded guilty to a misdemeanor FDCA violation and paid a criminal fine of $85 million for introducing Natrecor into interstate commerce for an off-label use.

“This case is an example of a drug company encouraging doctors to use a drug in a way that was unsupported by valid scientific evidence,” said First Assistant U.S. Attorney for the Northern District of California Brian Stretch.  “We are committed to ensuring that federal health care programs do not pay for such inappropriate uses, and that pharmaceutical companies market their drugs only for uses that have been proven safe and effective.”

Non-Monetary Provisions of the Global Resolution and Corporate Integrity Agreement

In addition to the criminal and civil resolutions, J&J has executed a five-year Corporate Integrity Agreement (CIA) with the Department of Health and Human Services Office of Inspector General (HHS-OIG).  The CIA includes provisions requiring J&J to implement major changes to the way its pharmaceutical affiliates do business.  Among other things, the CIA requires J&J to change its executive compensation program to permit the company to recoup annual bonuses and other long-term incentives from covered executives if they, or their subordinates, engage in significant misconduct.  J&J may recoup monies from executives who are current employees and from those who have left the company.  The CIA also requires J&J’s pharmaceutical businesses to implement and maintain transparency regarding their research practices, publication policies and payments to physicians.  On an annual basis, management employees, including senior executives and certain members of J&J’s independent board of directors, must certify compliance with provisions of the CIA.  J&J must submit detailed annual reports to HHS-OIG about its compliance program and its business operations.

“OIG will work aggressively with our law enforcement partners to hold companies accountable for marketing and promotion that violate laws intended to protect the public,” said Inspector General of the U.S. Department of Health and Human Services Daniel R. Levinson.  "Our compliance agreement with Johnson & Johnson increases individual accountability for board members, sales representatives, company executives and management.  The agreement also contains strong monitoring and reporting provisions to help ensure that the public is protected from future unlawful and potentially harmful off-label marketing."

Coordinated Investigative Effort Spans Federal and State Law Enforcement

This resolution marks the culmination of an extensive, coordinated investigation by federal and state law enforcement partners that is the hallmark of the Health Care Fraud Prevention and Enforcement Action Team (HEAT) initiative, which fosters government collaborations to fight fraud.  Announced in May 2009 by Attorney General Eric Holder and Health and Human Services Secretary Kathleen Sebelius, the HEAT initiative has focused efforts to reduce and prevent Medicare and Medicaid financial fraud through enhanced cooperation.

The criminal cases against Janssen and Scios were handled by the U.S. Attorney’s Offices for the Eastern District of Pennsylvania and the Northern District of California and the Civil Division’s Consumer Protection Branch.  The civil settlements were handled by the U.S. Attorney’s Offices for the Eastern District of Pennsylvania, the Northern District of California and the District of Massachusetts and the Civil Division’s Commercial Litigation Branch.  Assistance was provided by the HHS Office of Counsel to the Inspector General, Office of the General Counsel-CMS Division, the FDA’s Office of Chief Counsel and the National Association of Medicaid Fraud Control Units.

This matter was investigated by HHS-OIG, the Department of Defense’s Defense Criminal Investigative Service, the FDA’s Office of Criminal Investigations, the Office of Personnel Management’s Office of Inspector General, the Department of Veterans Affairs, the Department of Labor, TRICARE Program Integrity, the U.S. Postal Inspection Service’s Office of the Inspector General and the FBI.

One of the most powerful tools in the fight against Medicare and Medicaid financial fraud is the False Claims Act.  Since January 2009, the Justice Department has recovered a total of more than $16.7 billion through False Claims Act cases, with more than $11.9 billion of that amount recovered in cases involving fraud against federal health care programs.

The department enforces the FDCA by prosecuting those who illegally distribute unapproved, misbranded and adulterated drugs and medical devices in violation of the Act.  Since 2009, fines, penalties and forfeitures that have been imposed in connection with such FDCA violations have totaled more than $6 billion.

The civil settlements described above resolve multiple lawsuits filed under the qui tam, or whistleblower, provisions of the False Claims Act, which allow private citizens to bring civil actions on behalf of the government and to share in any recovery.  From the federal government’s share of the civil settlements announced today, the whistleblowers in the Eastern District of Pennsylvania will receive $112 million, the whistleblowers in the District of Massachusetts will receive $27.7 million and the whistleblower in the Northern District of California will receive $28 million.  Except to the extent that J&J subsidiaries have pleaded guilty or agreed to plead guilty to the criminal charges discussed above, the claims settled by the civil settlements are allegations only, and there has been no determination of liability.

FDA APPROVES GAZYVA FOR TREATING CHRONIC LYMPHOCYTIC LEUKEMIA

FROM:  U.S. FOOD AND DRUG ADMINISTRATION 
FDA approves Gazyva for chronic lymphocytic leukemia
Drug is first with breakthrough therapy designation to receive FDA approval

The U.S. Food and Drug Administration today approved Gazyva (obinutuzumab) for use in combination with chlorambucil to treat patients with previously untreated chronic lymphocytic leukemia (CLL).

CLL is a blood and bone marrow disease that usually gets worse slowly. According to the National Cancer Institute, 15,680 Americans will be diagnosed and 4,580 will die from the disease this year.

Gazyva works by helping certain cells in the immune system attack cancer cells. Gazyva is intended to be used with chlorambucil, another drug used to treat patients with CLL.

Gazyva is the first drug with breakthrough therapy designation to receive FDA approval. This designation was requested by the sponsor and granted soon after the biologic license application to support marketing approval was submitted to the FDA. The FDA can designate a drug a breakthrough therapy at the request of the sponsor if preliminary clinical evidence indicates the drug may offer a substantial improvement over available therapies for patients with serious or life-threatening diseases.

The FDA also granted Gazyva priority review because the drug demonstrated the potential to be a significant improvement in safety or effectiveness in the treatment of a serious condition. And the FDA granted Gazyva orphan product designation because it is intended to treat a rare disease.

“Today’s approval represents an important new addition to the treatments for patients with CLL,” said Richard Pazdur, M.D., director of the Office of Hematology and Oncology Products in the FDA’s Center for Drug Evaluation and Research. “This approval reflects the promise of the Breakthrough Therapy Designation program, allowing us to work collaboratively with companies to expedite the development, review and availability of important new drugs.”

Gazyva’s approval for CLL is based on a study of 356 participants in a randomized open-label multicenter trial comparing Gazyva in combination with chlorambucil to chlorambucil alone in participants with previously untreated CLL. Participants receiving Gazyva in combination with chlorambucil demonstrated a significant improvement in progression free survival: an average of 23 months compared with 11.1 months with chlorambucil alone.

The most common side effects observed in participants receiving Gazyva in combination with chlorambucil were infusion-related reactions, a decrease in infection-fighting white blood cells (neutropenia), a low level of platelets in the blood (thrombocytopenia), low red blood cells (anemia), pain in the muscles and bones (musculoskeletal pain), and fever (pyrexia).

Gazyva is being approved with a boxed warning regarding Hepatitis B virus reactivation and a rare disorder that damages the material that covers and protects nerves in the white matter of the brain (progressive multifocal leukoencephalopathy). These are known risks with other monoclonal antibodies in this class and rare cases were identified in participants on other trials of Gazyva. Patients should be advised of these risks and assessed for Hepatitis B virus and reactivation risk.

Gazyva is marketed by Genentech, a member of the Roche Group, based in South San Francisco, Calif.

FTC CHARGES MARKETER WITH DECEPTIVE ADVERTISING OF RAPID WEIGHT LOSS PRODUCT

FROM:  FEDERAL TRADE COMMISSION 
FTC Charges HCG Marketer with Deceptive Advertising

Defendants Promised Dietary Supplement Would Cause Substantial Weight Loss
The Federal Trade Commission has sued an Arizona man who markets HCG Platinum diet products by falsely claiming the products will cause consumers to lose substantial amounts of weight. Kevin Wright and his companies must respond to the complaint in federal court.
HCG, or human chorionic gonadotropin, is a hormone produced by the human placenta that, for decades, has been falsely promoted by various marketers for weight loss. In November 2011, Wright and six other HCG marketers received warning letters issued jointly by FDA and FTC staff, advising them that their HCG products are mislabeled drugs under the FDA Act, and warning that it is unlawful under the FTC Act to make weight-loss claims that are not supported by competent and reliable scientific evidence.

Marketing through retail outlets such as GNC, Rite Aid, and Walgreens, and through their own websites, Wright and his companies, HCG Platinum and Right Way Nutrition, LLC, promise consumers that HCG Platinum liquid drops will cause rapid and substantial weight loss, and they claim consumers will likely lose as much weight as the endorsers in their advertisements.

The defendants, who also make claims on Facebook, on product packaging, and in Internet pop-up ads and magazines, direct consumers to place the HCG concoctions under their tongues before meals and stick to a very low calorie diet of 500 to 800 calories per day. They typically charge between $60 and $149 for a thirty-day supply of one of their three HCG Platinum formulations.

The defendants market two of their three formulations as “homeopathic,” which means the listed ingredients are diluted to the point they are undetectable. On product packaging and in other advertising, they claim that the products cause consumers to lose a pound a day, are safe to use, and are clinically proven to burn fat, reduce weight, and lower cholesterol.

The defendants have sold more than $13 million of HCG Platinum since 2010. The FTC has asked the court to order the defendants to surrender the ill-gotten gains they received from their deceptive marketing of HCG Platinum products.

Consumers should be skeptical of advertisements that tout HCG as a weight-loss treatment.

For more information see the FDA video, Being Fooled by Empty Diet Promises.

The complaint also named seven relief defendants, who received money from sales of the HCG product, but had no active role in the alleged efforts to deceive consumers: Weekes Holdings, LLC; Primary Colors, LLC; KMATT Holdings, LLC; Nutrisport Holdings, LLC; Ty D. Mattingly; Julie Mattingly; and Annette Wright.

The Commission vote authorizing the staff to file the complaint was 4-0. The complaint was filed in the U.S. District Court for the District of Arizona on October 30, 2013.

NOTE: The Commission files a complaint when it has “reason to believe” that the law has been or is being violated and it appears to the Commission that a proceeding is in the public interest. The case will be decided by the court.

The Federal Trade Commission works for consumers to prevent fraudulent, deceptive, and unfair business practices and to provide information to help spot, stop, and avoid them. To file a complaint in English or Spanish, visit the FTC’s online Complaint Assistant or call 1-877-FTC-HELP (1-877-382-4357). The FTC enters complaints into Consumer Sentinel, a secure, online database available to more than 2,000 civil and criminal law enforcement agencies in the U.S. and abroad. The FTC’s website provides free information on a variety of consumer topics. Like the FTC on Facebook, follow us on Twitter, and subscribe to press releases for the latest FTC news and resources.

FDA LOOKING FOR REPORTS OF PETS GETTING SICK FROM JERKY PET TREATS

FROM:  U.S. FOOD AND DRUG ADMINISTRATION
Why Are Jerky Treats Making Pets Sick?

If you have a dog or cat that became ill after eating jerky pet treats, the Food and Drug Administration (FDA) would like to hear from you or your veterinarian.

The agency has repeatedly issued alerts to consumers about reports it has received concerning jerky pet treat-related illnesses involving 3,600 dogs and 10 cats in the U.S. since 2007. Approximately 580 of those pets have died.

To date, FDA’s Center for Veterinary Medicine (CVM) has conducted more than 1,200 tests, visited jerky pet treat manufacturers in China and collaborated with colleagues in academia, industry, state labs and foreign governments. Yet the exact cause of the illnesses remains elusive.

To gather even more information, FDA is reaching out to licensed veterinarians and pet owners across the country. "This is one of the most elusive and mysterious outbreaks we've encountered," says CVM Director Bernadette Dunham, DVM, Ph.D. "Our beloved four-legged companions deserve our best effort, and we are giving it."

In a letter addressing U.S. licensed veterinarians, FDA lists what information is needed for labs testing treats and investigating illness and death associated with the treats. In some cases, veterinarians will be asked to provide blood, urine and tissue samples from their patients for further analysis. FDA will request written permission from pet owners and will cover the costs, including shipping, of any tests it requests.

Meanwhile, a consumer fact sheet will accompany the letter to veterinarians so they can alert consumers to the problem and remind them that treats are not essential to a balanced diet. The fact sheet also explains to consumers how they can help FDA's investigation by reporting potential jerky pet treat-related illnesses online or by calling the FDA Consumer Complaint Coordinator for their state.

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What to Look Out For

Within hours of eating treats sold as jerky tenders or strips made of chicken, duck, sweet potatoes and/or dried fruit, some pets have exhibited decreased appetite, decreased activity, vomiting, diarrhea (sometimes with blood or mucus), increased water consumption, and/or increased urination.

Severe cases have involved kidney failure, gastrointestinal bleeding, and a rare kidney disorder. About 60 percent of cases involved gastrointestinal illness, and about 30 percent involved kidney and urinary systems.

The remaining cases reported various symptoms, such as collapse, convulsions or skin issues.

Most of the jerky treats implicated have been made in China. Manufacturers of pet foods are not required by U.S. law to state the country of origin for each ingredient in their products.

A number of jerky pet treat products were removed from the market in January 2013 after a New York State lab reported finding evidence of up to six drugs in certain jerky pet treats made in China. While the levels of these drugs were very low and it's unlikely that they caused the illnesses, FDA noted a decrease in reports of jerky-suspected illnesses after the products were removed from the market. FDA believes that the number of reports may have declined simply because fewer jerky treats were available.

Meanwhile, the agency urges pet owners to be cautious about providing jerky treats. If you do provide them and your pet becomes sick, stop the treats immediately, consider seeing your veterinarian, and save any remaining treats and the packaging for possible testing.


What FDA Is Doing

More than 1,200 jerky pet treat samples have been tested since 2011 for a variety of chemical and microbiological contaminants, from antibiotics to metals, pesticides and Salmonella. DNA testing has also been conducted, along with tests for nutritional composition.

In addition to continuing to test jerky pet treat samples within FDA labs, the agency is working with the Veterinary Laboratory Investigation and Response Network (Vet-LIRN), an FDA-coordinated network of government and veterinary diagnostic laboratories across the U.S. and Canada. (A summary of the tests is available on Vet-LIRN's webpage.)

Inspections of the facilities in China that manufacture jerky products associated with some of the highest numbers of pet illness reports did not identify the cause of illness. However, they did identify additional paths of investigation, such as the supply chain of some ingredients in the treats. Although FDA inspectors have found no evidence identifying the cause of the spate of illnesses, they did find that one firm used falsified receiving documents for glycerin, a jerky ingredient. Chinese authorities informed FDA that they had seized products at the firm and suspended its exports.

To identify the root cause of this problem, FDA is meeting regularly with regulators in China to share findings. The agency also plans to host Chinese scientists at its veterinary research facility to increase scientific cooperation.

FDA has also reached out to U.S. pet food firms seeking further collaboration on scientific issues and data sharing, and has contracted with diagnostic labs.

"Our fervent hope as animal lovers," says Dunham, "is that we will soon find the cause of—and put a stop to—these illnesses."

This article appears on FDA's Consumer Updates page, which features the latest on all FDA-regulated products.

Oct. 22, 2013

FDA'S APPROACH TO HARVESTING SAFE CLAMS

FROM:  U.S. FOOD AND DRUG ADMINISTRATION 
Novel Program Restarts Clam Harvest

One of the largest clam beds in the world closed in 1990 because people could get sick and even die from eating clams contaminated with a deadly marine toxin.

This year, however, a large portion of the area called Georges Bank, 62 miles off the coast of New England, reopened after the Food and Drug Administration (FDA) developed a new approach toward this risk to public health.

One major element involves having an FDA scientist train fishermen to perform sophisticated scientific tests on the clams while at sea, sometimes under extreme conditions.

"This program has almost doubled the number of quahog clams available on the market, and increases the availability of surf clams by about 40%," says David Wallace, a consultant for the seafood industry. "If it hadn't been for the FDA, these multi-billion dollar resources would be going to waste. It's good for fishermen, for consumers and for the economy." (The meat of quahog clams is tougher than surf clams and is often used in chowder, while surf clams often show up in raw bars.)

This is the story of how fishermen, industry representatives, state officials and multiple branches of the federal government worked together to create a novel plan that is allowing clams to be harvested from a major portion of Georges Bank—a vast submerged sandbank that extends from Massachusetts to Nova Scotia.

A Once Risky Catch
The story begins in the late 1980s, when harvest areas were temporarily closed due to the reports of toxins in surf clams from Georges Bank. After a brief reopening in early 1990, harvest areas were closed again when fishermen clamming on Georges Bank ate contaminated mussels caught while fishing for clams and became extremely ill.

The diagnosis: paralytic shellfish poisoning, caused by a toxin produced by Alexandrium algae. The toxic algae has been cited for centuries and is sometimes referred to as "red tide," even though not all red tides are toxic, and not all toxic blooms are red.

The toxin concentrates in the flesh of mollusks, including clams and mussels, and doesn't seem to hurt them. But in high enough concentrations, this potent toxin can temporarily paralyze humans. If this happens, the paralyzed person could die of asphyxiation if he or she is not put on life support until the toxins are flushed from the body. Cooking the mollusks does not neutralize the toxins.

FDA officials, who are responsible for the safety of seafood caught in federal waters, could not put scientists on board every clam fishing vessel far out at sea to test the clams for the toxin. It didn't make economic sense for fishermen to spend the time and money harvesting clams if they might arrive at the harbor, discover they had a boat filled with toxic clams, and then be responsible for safely disposing of them.

The 1990 closure of Georges Bank was a huge blow to the clam industry. The situation became even more dire in 2005, when a massive algal bloom near the New England shores temporarily closed another 15,000 square miles of ocean to clamming.

The clam industry, finding itself in peril, decided to invest the time and money required to find a solution, and began working with state and federal officials. After years of research on a harvesting procedure that could deliver safe clams at the dock, followed by an intense, years-long research and a pilot program, a huge portion of Georges Bank reopened in 2013 to clam fishermen who agreed to work under a new FDA procedure. This includes having fishermen take the FDA-provided training needed to conduct very precise scientific tests of clam samples while out to sea.

"There was a lot of skepticism. How would the fishermen react to listening to days of lectures from a young government scientist? Could they accurately conduct tests that sometimes even challenge lab scientists?" says FDA marine biotoxin expert Stacey DeGrasse, who has provided the FDA training.

"The project, however, is incredibly successful. The fishermen take great pride in performing the on-board lab tests and provide exact, pristine data," says DeGrasse.

The Tale of a Solution
The apex of the crisis in the clamming industry occurred just as FDA was conducting a research project with Woods Hole Oceanographic Institution. This extensive research project provided a greater understanding of the source of the toxins, movement of the toxins within the marine food web, the role of Alexandrium cyst (seed) beds as sources for future toxic algal blooms, and more.

Continued research efforts in this area focus on identifying effective early warning systems that could be used by state and federal regulators to determine when to open and close fishing areas. The policy side of the project is led by Paul Distefano, a consumer safety office in FDA's Center for Food Safety and Applied Nutrition.

One aspect of the project was aimed at training fishermen to use a field kit to test their product for the presence of dangerous marine toxins.

As one major aspect of the first test procedure, fishermen were first trained how to collect the correct number of representative samples of their catch and to shuck the clams without piercing the flesh. The samples were then mixed together in a kind of upscale blender to get an even, well-mixed consistency. Using household chemicals in the kit, the fishermen then learned to separate out any toxins that might be present. Finally, using something akin to a drugstore pregnancy test, the fishermen would test whether the potency of any toxin was at a dangerous level.

Tests of the field kit began at sea in 2007, but the kits provided too many results that were false positives. A better field kit was needed, and one used by lab scientists was identified. "I had doubts about how this was going to go," says DeGrasse. "The new kit was definitely more complicated, but I figured it was worth a try."

She worked with Abraxis, a test kit manufacturer, to make some adjustments. For one thing, the kit needed to be recalibrated to better target the toxins of concern. It also required modifications to make it usable at sea.

In 2009, after FDA had collected sufficient data, the new Abraxis kits were approved by the Interstate Shellfish Sanitation Conference (ISSC), a consortium of government officials, industry representatives and academics devoted to seafood safety. For a pilot program, the National Oceanic and Atmospheric Administration (NOAA) agreed to allow one fishing vessel to dredge for clams in the closed waters of Georges Bank for a year, a maximum of one time per week.

DeGrasse trained the fishermen for one day on land, then took the test kit out to sea and did further training on two-to-three-day clamming cruises. Once they were trained, the fishermen performed the onboard testing and sent portions of their samples to FDA for further scientific analyses. Later, when the vessel docked, state officials in Massachusetts performed a bioassay—an even more robust test that measures the overall potency of any toxins present.

That year, on just 37 fishing trips, that single vessel hauled in $2.7 million worth of surf clams that passed testing for toxins.

"The exciting part came when we put all the data together, and in 2011 the ISSC adopted the on-board screening protocol," says DeGrasse.

This year, NOAA reopened a large portion of Georges Bank to any fishermen who follow the established protocol, which includes on-board testing at sea by fishermen and back-up tests on land by government scientists.

"This has allowed the catch of literally billions of dollars worth of clams that otherwise would have died of old age," said Wallace. "It's a perfect example of how states, federal agencies and industry can work together to find solutions."

This article appears on FDA's Consumer Updates page, which features the latest on all FDA-regulated products.

Sept 17, 2013

FDA INVESTIGATES LEUKEMIA DRUG AFTER REPORTS OF BLOOD CLOTS

FROM:  U.S. FOOD AND DRUG ADMINISTRATION

FDA Drug Safety Communication: FDA investigating leukemia drug Iclusig (ponatinib) after increased reports of serious blood clots in arteries and veins
Safety Announcement

[10-11-2013]  The U.S. Food and Drug Administration (FDA) is investigating an increasing frequency of reports of serious and life-threatening blood clots and severe narrowing of blood vessels (arteries and veins) of patients taking the leukemia chemotherapy drug Iclusig (ponatinib).

Health care professionals should consider for each patient, whether the benefits of Iclusig treatment are likely to exceed the risks of treatment.

Patients taking Iclusig should seek immediate medical attention if they experience symptoms suggesting a heart attack such as chest pain or pressure, pain in their arms, back, neck or jaw, or shortness of breath; or symptoms of a stroke such as numbness or weakness on one side of the body, trouble talking, severe headache, or dizziness.

Iclusig is a prescription medicine used to treat adults diagnosed with chronic phase, accelerated phase, or blast phase chronic myeloid leukemia (CML) or Philadelphia chromosome-positive (Ph+) acute lymphoblastic leukemia (ALL), who are no longer benefiting from previous treatment or who did not tolerate other treatment.

At the time of Iclusig’s approval in December 2012, the drug label contained information about the risks of blood clots in the Boxed Warning and Warnings and Precautions sections.  In clinical trials conducted before approval, serious arterial blood clots occurred in 8 percent of Iclusig-treated patients, and blood clots in the veins occurred in 3 percent of Iclusig-treated patients.  In the most recent clinical trial data submitted by the manufacturer to FDA, at least 20 percent of all participants treated with Iclusig have developed blood clots or narrowing of blood vessels.

Data from clinical trials and postmarket adverse event reports show that serious adverse events have occurred in patients treated with Iclusig, including heart attacks resulting in death, worsening coronary artery disease, stroke, narrowing of large arteries of the brain, severe narrowing of blood vessels in the extremities, and the need for urgent surgical procedures to restore blood flow.  Other problems occurring with the drug’s use include congestive heart failure (CHF) and loss of blood flow to extremities resulting in tissue death requiring amputation.  Newly identified serious adverse reactions have also been reported involving the eyes, including decreased vision and clots in blood vessels of the eye. These adverse events were seen in all age groups treated and in those with and without cardiovascular risk factors.

FDA is providing this information to patients and health care professionals while it continues its investigation. We are actively working to further evaluate these adverse events and will notify the public when more information is available.

We urge health care professionals and patients to report side effects involving Iclusig to the FDA MedWatch program, using the information in the “Contact FDA” box at the bottom of this page.

FDA GRANTS ACCELERATED APPROVAL TO PERJETA FOR BREAST CANCER

FROM:  U.S. FOOD AND DRUG ADMINISTRATION 

The U.S. Food and Drug Administration today granted accelerated approval to Perjeta (pertuzumab) as part of a complete treatment regimen for patients with early stage breast cancer before surgery (neoadjuvant setting). Perjeta is the first FDA-approved drug for the neoadjuvant treatment of breast cancer.

Perjeta was approved in 2012 for the treatment of patients with advanced or late-stage (metastatic) HER2-positive breast cancer. HER2-positive breast cancers have increased amounts of the HER2 protein that contributes to cancer cell growth and survival.

Perjeta’s new use is intended for patients with HER2-positive, locally advanced, inflammatory or early stage breast cancer (tumor greater than 2 cm in diameter or with positive lymph nodes) who are at high risk of having their cancer return or spread (metastasize) or of dying from the disease. It is to be used in combination with trastuzumab and other chemotherapy prior to surgery and, depending upon the treatment regimen used, may be followed by chemotherapy after surgery. Following surgery, patients should continue to receive trastuzumab to complete one year of treatment.

FDA APPROVES BRINTELLIX TO TREAT ADULT MAJOR DEPRESSIVE DISORDER

FROM:  U.S. FOOD AND DRUG ADMINISTRATION 
The U.S. Food and Drug Administration today approved Brintellix (vortioxetine) to treat adults with major depressive disorder.

Major depressive disorder (MDD), commonly referred to as depression, is a mental disorder characterized by mood changes and other symptoms that interfere with a person's ability to work, sleep, study, eat and enjoy once-pleasurable activities. Episodes of depression often recur throughout a person's lifetime, although some may experience a single occurrence.

Other signs and symptoms of MDD include loss of interest in usual activities, significant change in weight or appetite, insomnia or excessive sleeping (hypersomnia), restlessness/pacing (psychomotor agitation), increased fatigue, feelings of guilt or worthlessness, slowed thinking or impaired concentration, and suicide attempts or thoughts of suicide. Not all people with MDD experience the same symptoms.

FDA APPROVES GENERIC VERSION OF XELODA CHEMOTHERAPY PILL

FROM:  U.S. FOOD AND DRUG ADMINISTRATION 
FDA approves first generic capecitabine to treat colorectal and breast cancers

The U.S. Food and Drug Administration today approved the first generic version of Xeloda (capecitabine), an oral chemotherapy pill used to treat cancer of the colon or rectum (colorectal cancer) that has spread to other parts of the body (metastatic), and metastatic breast cancer.

Teva Pharmaceuticals USA has gained FDA approval to market generic capecitabine in 150 and 500 milligram strengths.

“Generic drugs are important options that allow greater access to health care for all Americans,” said Kathleen Uhl, M.D., acting director of the Office of Generic Drugs in the FDA’s Center for Drug Evaluation and Research. “This medication is widely used by people living with cancer, so it is important to have access to affordable treatment options.”

According to the National Cancer Institute, it is estimated that 1.6 million people in the United States will be diagnosed with and 580,000 will die of cancer in 2013. It is estimated that 142,820 people will be diagnosed with and 50,830 will die of cancer of the colon and rectum in 2013. An estimated 232,340 women will be diagnosed with and 39,620 women will die of cancer of the breast in 2013.

In the clinical trials for Xeloda, the most commonly observed adverse reactions included: diarrhea; vomiting; nausea; pain, redness, swelling, or sores in the mouth; hand-and-foot syndrome (pain, swelling, or redness of hands or feet that prevents normal activity); and fever or infection.

It is important that the prescriber know if the patient is also taking a medicine used to thin the blood, such as warfarin. Capecitabine could increase the effect of this medicine, possibly leading to serious side effects. Capecitabine has a boxed warning to alert health care professionals and patients about this risk.

Generic drugs approved by the FDA have the same high quality and strength as brand-name drugs. Generic drug manufacturing and packaging sites must pass the same quality standards as those of brand-name drugs.

Information about the availability of generic capecitabine can be obtained from Teva.

ISSUE WITH NERVE AGENT ANTIDOTE AUTOINJECTOR

FROM:  U.S. DEFENSE DEPARTMENT 
DOD, Manufacturer Address Issue with Antidote Autoinjector
By Cheryl Pellerin
American Forces Press Service

WASHINGTON, Sept. 13, 2013 - Defense Department and interagency officials are working closely with the Maryland-based manufacturer of an autoinjector for deployed troops that contains a two-drug antidote for some kinds of nerve agents, a military official said.

In March the company, Meridian Medical Technologies, a Pfizer Inc. subsidiary, found after an internal inspection that a small number of the autoinjectors -- seven out of 1,000 -- were not completely filled with antidote. The company also notified the Defense Department in March.

Since then, Meridian has been working with the Food and Drug Administration, which licensed the product in 2006, to improve product-quality issues in the manufacturing process, and with government agencies on a priority replacement plan.

There are no plans to recall the equivalent civilian product, called DuoDote, or the military product, called Antidote Treatment Nerve Agent-Autoinjector, or ATNAA, the official said. In the meantime, nothing has changed for service members in the field who are issued the product when a threat looms, the military official said.


With the current ATNAA product, the military official said, "warfighters are protected and there is no operational impact. The FDA has opined that all autoinjectors are safe and effective and can be used under current tactics, techniques and procedures."

The autoinjector is a spring-loaded syringe designed to overcome the hesitation someone might show when self-injecting even a small needle. To user removes a cap on the back, puts the front end on the outer thigh or buttocks, pushes until the device activates, then holds it in place for 10 seconds.

The ATNAA autoinjector has two internal chambers, one on top of the other. The top chamber contains the drug atropine, and the bottom chamber holds pralidoxime chloride. When the injector activates, the drugs flow together through a syringe and into the body.

Nerve agents are fast-working and deadly, andinhibit a range of physiological processes in the nervous system, causing pinpoint pupils, eye pain, sweating, drooling, tearing, vomiting and seizures.

Atropine reduces secretions in the mouth and respiratory passages, relieves respiratory passage constriction and spasms, and may reduce respiratory paralysis caused by toxic agents on the central nervous system.

Pralidoxime chloride relieves paralysis of respiration muscles and is always used with atropine to treat nerve-agent poisoning.

For the Defense Department to date, Meridian has put 1.1 million ATNAA autoinjectors through a process of remediation that includes first a visual examination by trained technicians and then weighing the autoinjectors to make sure they're properly filled with antidote, the military official said, adding that improperly filled devices are being rejected.

The Defense Logistics Agency is working through the contractual details about how Meridian will replace the defective devices, the official added.

"There are two lines of effort: new manufacturing and remediation. We're hopeful the FDA will approve the enhancements to [Meridian's] manufacturing process within the next 12 weeks, and then as soon as DLA works through the details on acceptance of the remediated product, it will be available [to DOD]," the military official said.

In addition to DLA, the Joint Program Executive Office forChemical and Biological Defense is working in close coordination with the FDA, the Army Medical Research and Materiel Command, and the Army Office of the Surgeon General to help resolve the issue.

The military official said Meridian is working closely with regulators from the FDA and internally to make sure a more rigorous quality-control process is in place so the problem won't happen again.

"The company has made a good-faith effort to remediate the issues, both with current product and in the future," Pentagon spokeswoman Jennifer D. Elzea said, "so from the department's perspective, they've been cooperative."

FDA EVALUATES TECHNOLOGIES TO MAKE BLOOD SUPPLY SAFER

FROM:  U.S. FOOD AND DRUG ADMINISTRATION 

Every two seconds in the U.S., someone needs a blood transfusion or blood product—people of all ages who are injured, need surgery or who are suffering from illness. The Food and Drug Administration's (FDA) primary responsibility with regard to blood and blood products is to assure the safety of patients who receive these life-saving products. FDA is at the forefront of evaluating and encouraging innovative technologies designed to identify and minimize the risks to people who receive transfusions, such as the transmission of infectious disease, while maintaining a safe and adequate supply.

Richard Davey, M.D., is director of the Division of Blood Applications, Office of Blood Research and Review, at FDA. He discusses advances in the field, contingency plans during disasters and why—and when—to give blood.

Q: There have been many improvements in transfusion practice since the modern era of blood transfusion began in 1900. What's on the horizon?

A: We're excited about many developments, including a new red blood cell testing technology aimed at patients with illnesses that require frequent transfusions, for example sickle cell anemia. These patients sometimes develop antibodies that complicate finding compatible blood for transfusion.

A new FDA laboratory is evaluating this new technology which identifies the genetic characteristics of a patient's red blood cells so they can be more precisely matched to a donor. FDA is encouraging submissions from industry for these molecular test kits. It's an important breakthrough.

Exciting research is also progressing on technologies that will significantly reduce any bacteria, viruses and parasites that may be in blood. These technologies would complement existing tests for these infectious agents, thus making a safe blood supply even safer.

Q: Isn't the blood supply already safe?

A: The United States is recognized as having one of the safest blood supplies in the world, but assuring the safety and availability of blood products still poses challenges. The HIV risk to recipients is now only about 1 in every 2 million units of blood transfused in the USA, but it's still not zero. We test all blood for HIV, hepatitis B and C, West Nile virus and the parasite that causes Chagas disease, among other infectious agents. Blood found to contain any of these pathogens is discarded and, in most cases, the individual is notified and deferred from further donation.

Q: Is artificial blood possible?

A: Companies are working to develop oxygen carriers that could substitute for red blood cells. We're working with these companies and remain hopeful that one or more of these technologies eventually will prove to be safe and effective.

Q: How much blood is needed in the U.S.?

A: About 15 million units of red blood cells are drawn every year for transfusion to about five million recipients. In recent years, the demand for red blood cells has declined, primarily because doctors are learning to transfuse more scientifically and use blood only when necessary. However, challenges remain. In June, for example, the American Red Cross had almost 50,000 fewer donors than expected. Type O negative red cells, which can be transfused to people of all blood types, is the blood type most likely to be in short supply, but there is a need for donors of all blood types, all the time.

The American Red Cross and independent blood centers affiliated with America's Blood Centers each collect about 45% of the blood supply, with the remainder collected by hospital blood banks.

Q: At the Boston Marathon, 264 people were injured, creating an unexpected demand for blood. Did that cause a supply problem?

A: Boston has an excellent triage system so casualties were spread among several hospitals, which also spread the need for blood. In case of a disaster such as the marathon bombing, an interagency task force mobilizes to move blood to where it is needed.

Q: During disasters, many people volunteer to donate blood. Is that helpful?

A: It's a good and noble response, but we need donors every day to meet ongoing requirements for blood. It takes two to three days to fully test and qualify blood for transfusion. Therefore, it is the blood that is fully tested and available for transfusion that is used at the time of an emergency. The people donating today will be the heroes if a disaster occurs next week.

After 9/11, for example, many people donated. However, little of the additional blood was needed, and some of the donated blood expired and had to be discarded. The best response during a major disaster is to have already qualified as a regular blood donor and to have records on file at the blood center. Then the blood center can call you when your blood type is most needed. And, as mentioned above, become a regular blood donor for everyday patient needs and to have your blood available if an emergency occurs.

Q. What are the different components of blood, and how are they used?

A. Whole blood can be divided into several components, each of which can be important to a patient in need. Red blood cells carry oxygen, and are important to correct bleeding or to compensate for inadequate production of these cells. Blood platelets are small particles that are important for normal blood clotting to occur. They are often used in cancer patients, when the disease or the treatment interferes with the normal production of these elements. Blood plasma is the yellow fluid that remains when the red cells and other particles are removed. Plasma is also important for normal blood clotting to occur. It can be transfused without modification, or further processed into important products such as gamma globulin or albumin.

Q: How long does blood last?

A: It's different for each of the blood components. Red blood cells can be stored for six weeks as a liquid. Blood platelets can be stored only for five days. Blood plasma can be frozen for use up to one year. New additives, preservatives and storage techniques are being developed to help extend expiration dates.

Q: Of those eligible to donate, how many do so?

A: We estimate that about 45% of the population is eligible to donate blood. However, only about 4% actually do so, and 75% of those are repeat donors.

Donating blood is extremely safe for donors, with each needle and blood bag used only once. About one pint of whole blood is collected in a standard donation, which is about 10% of an average adult's total blood volume. Alternatively, most blood centers have instruments that allow a donor to specifically donate red cells, platelets and/or plasma, according to current needs. The body replaces the donated blood within a short time. Donors get a "mini-physical" and cookies. Most importantly, they know that their donation can help several patients who require these life-saving products. They truly are giving the "gift of life."

This article appears on FDA's Consumer Updates page, which features the latest on all FDA-regulated products.

Sept 16, 2013

NEW FDA ANNOUNCEMENT REGARDING TREATMENT OF PAIN WITH OPIOID ANALGESICS

FROM:  FOOD AND DRUG ADMINISTRATION

The Division of Drug Information (DDI) is CDER's focal point for public inquiries. We serve the public by providing information on human drug products and drug product regulation by FDA.

The U.S. Food and Drug Administration announced class-wide safety labeling changes and new postmarket study requirements for all extended-release and long-acting (ER/LA) opioid analgesics intended to treat pain.

Given the serious risks of using ER/LA opioids, the class-wide labeling changes, when final, will include important new language to help health care professionals tailor their prescribing decisions based on a patient’s individual needs.

The updated indication states that ER/LA opioids are indicated for the management of pain severe enough to require daily, around-the-clock, long-term opioid treatment and for which alternative treatment options are inadequate.

The updated indication further clarifies that, because of the risks of addiction, abuse, and misuse, even at recommended doses, and because of the greater risks of overdose and death, these drugs should be reserved for use in patients for whom alternative treatment options (e.g., non-opioid analgesics or immediate-release opioids) are ineffective, not tolerated, or would be otherwise inadequate to provide sufficient management of pain; ER/LA opioid analgesics are not indicated for as-needed pain relief.

FDA LOOKS AT HEALTH AFFECTS OF ARSENIC IN RICE

FROM:  U.S. FOOD AND DRUG ADMINISTRATION 
FDA Explores Impact of Arsenic in Rice

The Food and Drug Administration (FDA) has taken a major step towards learning whether levels of arsenic in rice and rice products pose a risk to public health.

The agency has collected a total of more than 1,300 samples of rice and rice products and has tested them for both total arsenic and inorganic arsenic, the more toxic form. FDA scientists have determined that the levels of inorganic arsenic found in the samples are too low to cause immediate health damage.

In the rice grains, the average levels of inorganic arsenic ranged from 2.6 to 7.2 micrograms per serving, with instant rice at the low end of the range and brown rice at the high end. In rice products, the average levels of inorganic arsenic ranged from 0.1 to 6.6 micrograms per serving, with infant formula at the low end of the range and rice pasta at the high end. (A microgram is one-millionth of a gram; serving sizes varied with the product types.)

But what about the long-term impact? After all, rice is a food that people eat over the course of a lifetime.

The next step for FDA will be to conduct a comprehensive risk assessment, explains Suzanne C. Fitzpatrick, Ph.D., the senior advisor for toxicology in FDA's Center for Food Safety and Applied Nutrition (CFSAN). This analysis of the health risk associated with eating rice and rice products will be the foundation of future FDA actions.

"These are the next steps. To look at exposure levels, to analyze the risk, and determine how to minimize that risk for the overall safety of consumers, including vulnerable groups like children and pregnant women," says Fitzpatrick.

"We must take one step at a time and stay true to our methodological approach," says Michael R. Taylor, J.D., deputy commissioner for foods and veterinary medicine. "We can't get ahead of the science."

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Why Rice?
"One of the things we need to emphasize is that arsenic is a naturally occurring contaminant, and because it's in soil and water, it's going to get into food," says Fitzpatrick. "It's not something that we can just pull off the market."

Arsenic is a chemical element distributed in the Earth's crust. Human activities such as fuel burning, mining and the use of arsenic compounds in pesticides have also added arsenic to the environment. But Fitzpatrick says that even if you stripped all human contributions, there would still be arsenic in food.

And rice is particularly vulnerable. "Rice is grown in water and takes in arsenic. You're going to see greater levels in rice than in other foods," she says.

FDA has been monitoring arsenic levels in foods for more than 20 years, but Fitzpatrick says there have been advances in testing that allow FDA to get much more detailed information.

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The Story So Far
FDA consumer safety officers collected samples from retail outlets across the country. In addition to rice itself, these samples cover most types of rice-based foods in the American diet, including cereals, cakes, beverages, snack bars and infant and toddler foods.

These samples were then analyzed in FDA labs, in addition to some labs contracted by the agency to do this work. Fitzpatrick says the laboratory workers were required to undergo training in new chemical testing called "speciation." This testing enables the labs to look beyond just organic vs. inorganic to all the different species of arsenic present in the samples.

"It's a very complicated process and it involves a lot of people," Fitzpatrick says. "We're working very hard to get the best possible scientific answers."

Meanwhile, FDA was studying arsenic in other ways. Researchers examined studies of populations exposed to high levels of arsenic in such countries as Chile, Taiwan and Bangladesh. They looked at rates of cancer and diseases such as diabetes and cardiovascular illnesses.

The researchers had to consider how the data about these highly exposed cultures would apply to American consumers.

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What's Next?
Next is the risk assessment. All of this information will now be considered by FDA risk managers, Fitzpatrick says. These experts will look at the hazards that arsenic presents in rice products and the degrees to which people are exposed.

The risk assessment teams will also consider if certain segments of the population are more vulnerable because of their lifestyle (such as ethnic groups that eat a lot of rice) or life stage (pregnant women and children).

They will then assess the public health risk from arsenic in rice.

The risk assessment will take a number of months to complete. After an expert review, the assessment will be available for public comment. "This is an important issue for us," say Fitzpatrick. "Consumers need the best information that we can get them."

FDA is working with federal partners—including the U.S. Department of Agriculture, the Environmental Protection Agency, the National Institute of Environmental Health Sciences, and the Centers for Disease Control and Prevention—as well as with industry scientists, consumer groups and others to further study the issue of arsenic in rice and evaluate ways to reduce exposure, such as through changes in growing or manufacturing practices.

And FDA is conducting additional sampling to broaden its data on the levels of arsenic in all infant and toddler products.

This article appears on FDA's Consumer Update page, which features the latest on all FDA-regulated products.

Sept. 6, 2013

FDA WORKS TO UNDERSTAND THE SAFETY OF ANESTHESIA FOR INFANTS AND YOUNG CHILDREN

FROM:  U.S. FOOD AND DRUG ADMINISTRATION 
When infants or young children need surgery, does anesthesia affect their developing brains?

With more than 1 million children under age 4 requiring anesthesia for surgery in the United States each year, the Food and Drug Administration (FDA) and other health organizations are working together to answer this question.

Previous scientific studies in young animals have shown that commonly used anesthetics can be harmful to the developing brain. However, results have been mixed in children. Some studies of infants and young children undergoing anesthesia have reported long-term deficits in learning and behavior; other studies have not.

These conflicting results show that more research is needed to fully understand the risks anesthesia may pose to very young patients.

To close these research gaps, FDA and the International Anesthesia Research Society (IARS) started an initiative called SmartTots (Strategies for Mitigating Anesthesia-Related neuroToxicity in Tots). SmartTots seeks to ensure that children under age 4 will be as safe as possible when they need anesthesia during surgery. Studies have shown that this is a period of significant brain development in young children.

"Our hope is that research funded through SmartTots will help us design the safest anesthetic regimens possible," says Bob Rappaport, M.D., director of the Division of Anesthesia, Analgesia and Addiction Products at FDA. "This research can potentially foster the development of new and safer anesthetic drugs for use in pediatric medicine."

According to SmartTots steering committee co-chair James Ramsay, M.D., young children usually do not undergo surgery unless the procedure is vital to their health. "Therefore, postponing a necessary procedure may itself lead to significant health problems and may not be an option for the majority of children," Ramsey says.

WYETH PHARMACEUTICALS AGREES TO PAY $490.9 MILLION FOR MARKETING DRUG FOR UNAPPROVED USES

FROM:  U.S. DEPARTMENT OF JUSTICE 

Tuesday, July 30, 2013
Wyeth Pharmaceuticals Agrees to Pay $490.9 Million for Marketing the Prescription Drug Rapamune for Unapproved Uses

Wyeth Pharmaceuticals Inc., a pharmaceutical company acquired by Pfizer, Inc. in 2009, has agreed to pay $490.9 million to resolve its criminal and civil liability arising from the unlawful marketing of the prescription drug Rapamune for uses not approved as safe and effective by the U.S. Food and Drug Administration (FDA), the Justice Department announced today.  Rapamune is an “immunosuppressive” drug that prevents the body’s immune system from rejecting a transplanted organ.

 “FDA’s drug approval process ensures companies market their products for uses proven safe and effective,” said Stuart F. Delery, Acting Assistant Attorney General for the Justice Department’s Civil Division.  “We will hold accountable those who put patients’ health at risk in pursuit of financial gain.”

 The Federal Food, Drug and Cosmetic Act (FDCA) requires a company such as Wyeth to specify the intended uses of a product in its new drug application to the FDA.  Once approved, a drug may not be introduced into interstate commerce for unapproved or “off-label” uses until the company receives FDA approval for the new intended uses.  In 1999, Wyeth received approval from the FDA for Rapamune use in renal (kidney) transplant patients.  However, the information alleges, Wyeth trained its national Rapamune sales force to promote the use of the drug in non-renal transplant patients.  Wyeth provided the sales force with training materials regarding non-renal transplant use and trained them on how to use these materials in presentations to transplant physicians.  Then, Wyeth encouraged sales force members, through financial incentives, to target all transplant patient populations to increase Rapamune sales.

“The FDA approves drugs for certain uses after lengthy clinical trials,” said Sanford Coats, U.S. Attorney for the Western District of Oklahoma.  “Compliance with these approved uses is important to protect patient safety, and drug companies must only market and promote their drugs for FDA-approved uses.  The FDA approved Rapamune for limited use in renal transplants and required the label to include a warning against certain uses.  Yet, Wyeth trained its sales force to promote Rapamune for off-label uses not approved by the FDA, including ex-renal uses, and even paid bonuses to incentivize those sales.  This was a systemic, corporate effort to seek profit over safety.  Companies that ignore compliance with FDA regulations will face criminal prosecution and stiff penalties.”

Wyeth has pleaded guilty to a criminal information charging it with a misbranding violation under the FDCA.  The resolution includes a criminal fine and forfeiture totaling $233.5 million.  Under a plea agreement, which has been accepted by the U.S. District Court in Oklahoma City, Wyeth has agreed to pay a criminal fine of $157.58 million and forfeit assets of $76 million.

The resolution also includes civil settlements with the federal government and the states totaling $257.4 million.  Wyeth has agreed to settle its potential civil liability in connection with its off-label marketing of Rapamune.  The government alleged that Wyeth violated the False Claims Act, from 1998 through 2009, by promoting Rapamune for unapproved uses, some of which were not medically accepted indications and, therefore, were not covered by Medicare, Medicaid and other federal health care programs.  These unapproved uses included non-renal transplants, conversion use (switching a patient from another immunosuppressant to Rapamune) and using Rapamune in combination with other immunosuppressive agents not listed on the label.  The government alleged that this conduct resulted in the submission of false claims to government health care programs.  Of the amounts to resolve the civil claims, Wyeth will pay $230,112,596 to the federal government and $27,287,404 to the states.  

“Wyeth’s conduct put profits ahead of the health and safety of a highly vulnerable patient population dependent on life-sustaining therapy,” said Antoinette V. Henry, Special Agent in Charge, Metro-Washington Field Office, FDA Office of Criminal Investigations.  “FDA OCI is committed to working with the Department of Justice and our law enforcement counterparts to protect public health.”

Pfizer is currently subject to a Corporate Integrity Agreement (CIA) with the Department of Health and Human Services’ Office of Inspector General that it entered in connection with another matter in 2009, shortly before acquiring Wyeth.  The CIA covers former Wyeth employees who now perform sales and marketing functions at Pfizer.  Under the CIA, Pfizer is subject to exclusion from federal health care programs, including Medicare and Medicaid, for a material breach of the CIA, and the company is subject to monetary penalties for less significant breaches.

“We are committed to enforcing the laws protecting public health, taxpayers and government health programs, and to promoting effective compliance programs,” said Daniel R. Levinson, Inspector General, Department of Health and Human Services.  “Our integrity agreement with Pfizer, which acquired Wyeth, includes required risk assessments, a confidential disclosure program, and auditing and monitoring to help prospectively identify improper marketing.”

 The civil settlement resolves two lawsuits pending in federal court in the Western District of Oklahoma under the qui tam, or whistleblower, provisions of the False Claims Act, which allow private citizens to bring civil actions on behalf of the government and share in any recovery.  The first action was filed by a former Rapamune sales representative, Marlene Sandler, and a pharmacist, Scott Paris.  The second action was filed by a former Rapamune sales representative, Mark Campbell.  The whistleblowers’ share of the civil settlement has not been resolved.

 "The success obtained in this case is an excellent example of how we address the threats to our nation’s health care system; the importance of the public reporting of fraud, waste, or abuse; and the significant results that can be obtained through multiple agencies cooperating in investigations,” said James E. Finch, Special Agent in Charge of the Oklahoma City Division of the FBI.

 The criminal case was handled by the U.S. Attorney’s Office for the Western District of Oklahoma (USAO) and the Justice Department’s Civil Division, Consumer Protection Branch.  The civil settlement was handled by USAO and the Justice Department’s Civil Division, Commercial Litigation Branch.  The Department of Health and Human Services’ (HHS) Office of Counsel to the Inspector General; the HHS Office of General Counsel, Center for Medicare and Medicaid Services; the FDA’s Office of Chief Counsel; and the National Association of Medicaid Fraud Control Units.  These matters were investigated by the FBI; the FDA’s Office of Criminal Investigation; HHS’ Office of Inspector General, Office of Investigations and Office of Audit Services; the Defense Criminal Investigative Service; the Office of Personnel Management’s Office of Inspector General and Office of Audit Services; the Department of Veterans’ Affairs’ Office of Inspector General; and TRICARE Program Integrity.

 Except for conduct admitted in connection with the criminal plea, the claims settled by the civil agreement are allegations only, and there has been no determination of civil liability.  The civil lawsuits are captioned United States ex rel. Sandler et al v. Wyeth Pharmaceuticals, Inc., Case No. 05-6609 (E.D. Pa.) and United States ex rel. Campbell v. Wyeth, Inc., Case No. 07-00051 (W.D. Okla.).

MAN AND COMPANY CHARGED WITH MAKING MISTATEMENTS OF FDA'S VIEW OF COMPANY

FROM: U.S. SECURITIES AND EXCHANGE COMMISSION

Washington, D.C., June 26, 2013 — The Securities and Exchange Commission today announced that it filed fraud charges on Tuesday against Burbank, Calif.-based Imaging3, Inc., and its founder and chief executive Dean Janes for misleading shareholders about the Federal and Drug Administration (FDA)’s view of the company’s medical device

The SEC’s complaint alleges that Janes held a conference call with investors in November 2010 after the FDA denied clearance for Imaging3, Inc. to market its proprietary scanner, which provides three-dimensional images for use in medical diagnosis. The denial was the product’s third, as the FDA denied clearance in 2008 and earlier in 2010. Even though the FDA cited concerns about the safety of the device and the quality of the images, Janes told investors that the FDA’s issues were "not substantive" and largely "administrative."

"Shareholders have a right to trust corporate officers to tell them the truth about the business. When CEOs abuse that trust and make misstatements, innocent shareholders are victimized," said Michele Wein Layne, Regional Director of the SEC’s Los Angeles Regional Office. "The SEC will hold corporate officers accountable for misleading shareholders."

According to the SEC’s complaint, filed in the U.S. District Court for the Central District of California, on the conference call, Janes did not discuss the issues raised by the FDA in an October 2010 letter, such as the device’s potential for over-heating, and the fact that some sample images the company submitted were "scientifically invalid and useless."

Even when asked on the call whether any of the FDA’s concerns were "safety-related" or involved image quality, Janes said, "Nope," and that there was "really and honestly not one question about the technology or its consistency. It just doesn’t make sense to me."

After an investor obtained the FDA’s denial letter and posted it on an Internet blog in early 2011, Janes used his personal Facebook page in another effort to mischaracterize the denial, the SEC alleged. Janes and his company didn’t officially issue the full text of the denial letter until earlier this year, more than two years after the call to discuss it.

The SEC's action charges Imaging3, Inc. and Janes with fraud and seeks a court order to bar them from future violations of federal securities laws, require them to pay civil monetary penalties, and bar Janes from serving as a public company officer or director.

Alka Patel and Katharine Zoladz of the Los Angeles Regional Office conducted the SEC’s investigation and David Van Havermaat will lead the litigation.