------------------------------------------------------------------------ FDA Consumer magazine VOL. 30 No. 8 OCTOBER 1996 ------------------------------------------------------------------------ Features Saving Our Children from Tobacco Every day, almost 3,000 young people start smoking. Nearly 1,000 of them will have their lives cut short due to smoking-related illness. To protect America's children from this number one cause of preventable death and illness, FDA has issued a landmark regulation intended to make cigarettes and smokeless tobacco less available to kids, and less alluring. New Devices Aim at Improving Pap Test Accuracy Methods to improve diagnostic accuracy of Pap tests are among the tools for fighting cervical cancer, a very curable disease if caught early. Colds and Flu: Time Only Sure Cure Chicken soup, vitamin C, hand-washing, and cough and cold medications are among the many ways some folks say can prevent or treat colds and flu. Which ones work? Help for People with Paget's Disease Many people dismiss symptoms of this bone disease as part of the aging process. But effective treatments are available and are best begun early. Inside FDA: Office of Women's Health This FDA office has funded more than 50 projects since it was established in 1994. And its $2 million annual budget promises further support for research and education on a number of women's health topics. Probing the Pancreas Diabetes and cystic fibrosis are just two of the diseases that involve the pancreas. Various treatments are available for these conditions. ------------------------------------------------------------------------ Departments Updates The latest information on FDA-related issues, gathered from FDA Press Releases, Talk Papers, and other sources. Notebook A potpourri of items of interest gathered from the Federal Register and other sources. Investigators' Reports Selected cases illustrating regulatory and administrative actions--such as inspections, recalls, seizures, and court proceedings--by FDA's regional and district offices across the country Summaries of Court Actions Cases involving seizure, criminal and injunction proceedings. ------------------------------------------------------------------------ Saving Our Children from Tobacco President Clinton announced on Aug. 23 the nation's first comprehensive program to prevent children and adolescents from smoking cigarettes or using smokeless tobacco and beginning a lifetime of nicotine addiction. The president's announcement came a little more than a year after the Food and Drug Administration issued its proposed rule to reduce the access and appeal of tobacco products for children and adolescents. The FDA rule-making on children and tobacco prompted the largest outpouring of public response in the agency's history, with more than 95,000 individual comments received, totaling more than 700,000 pieces of mail when form letters are counted. The final rule was published in the Federal Register of Aug. 28, 1996. For more information on the final rule and related documents, see FDA's Children and Tobacco Home Page. Each day, almost 3,000 young people in the United States become regular smokers, and nearly 1,000 of them will die prematurely from diseases related to tobacco use. Each year, more than 400,000 Americans die from smoking-related diseases, more Americans than are killed each year by AIDS, alcohol, car accidents, murders, suicides, illegal drugs, and fires combined. In the last four years, the United States has experienced dramatic increases in tobacco use by youngsters. Between 1991 and 1995, the percentage of eighth- and 10th-graders who smoke increased 34 percent. In 1995, more than a third of 12th-graders reported smoking in the past month, and daily smoking in that group was up to 21.6 percent. Among 10th-graders, current use was up to 27.9 percent, and daily use was up to 16.3 percent. President Clinton's goal is to cut in half tobacco use by children and adolescents over the next seven years. "This is the most important public health initiative of our generation," said Health and Human Services Secretary Donna E. Shalala. "Our children's futures are at stake. President Clinton's action will ensure that children get their information about tobacco from their parents--and not from Joe Camel." The president's initiative to protect children is based on the final FDA rule that will make it harder for young people to buy cigarettes and smokeless tobacco and will reduce the appeal of tobacco products to children under 18. The rule is based on the agency's finding that cigarettes and smokeless tobacco products are delivery devices for nicotine, an addictive drug. In addition to the rule, FDA will propose to require tobacco companies to educate children and adolescents about the health risks of tobacco use as part of the president's initiative. This national mass media campaign would be monitored for its effectiveness. Cigarettes and smokeless tobacco products remain legal products that can be marketed and sold to adults, 18 years and older. "Nicotine addiction is a pediatric disease that often begins at 12, 13, and 14 only to manifest itself at 16 and 17 when these children find they cannot quit," said Commissioner of Food and Drugs David A. Kessler, M.D. "By then our children have lost their freedom and face the prospect of lives shortened by terrible diseases." The president's initiative follows the recommendations of major medical and scientific organizations such as the American Medical Association and National Academy of Science's Institute of Medicine. It is a prevention strategy based on reducing children's access to tobacco products and limiting the appeal of these products to children. The tobacco industry spends more than $6 billion annually on advertising and promotion. Besides the final rule, FDA will propose to require tobacco companies to provide strong educational messages for children on the real dangers of smoking and using smokeless tobacco. This national multimedia campaign would include television spots, and it would be monitored for its effectiveness. FDA intends to begin consultations about this campaign with the nation's six tobacco companies with a significant share of sales to children. Under Section 518 of the Federal Food, Drug, and Cosmetic Act, the FDA may require companies to inform consumers about the unreasonable health risks of their products. "We have to tell our children the truth about the diseases caused by smoking," Kessler said. "For too long we have sent conflicting messages to our children and then have acted surprised when they begin to smoke." In reviewing the public comments and developing a final rule, FDA made a number of changes to more narrowly tailor provisions to children. For instance, there was little evidence presented that mail-order sales are used by children and adolescents, while they are used by adults in rural areas. Similarly, vending machines in facilities totally inaccessible to persons under 18 will accommodate adults while preventing easy access by young people. The FDA rule reduces children's easy access to tobacco products by: * Requiring age verification by photo ID for anyone under the age of 27 purchasing tobacco products. * Banning vending machines and self-service displays except in "adult" facilities where children are not allowed, such as certain nightclubs totally inaccessible to anyone under 18. * Banning free samples and the sale of single cigarettes and packages containing fewer than 20 cigarettes. The FDA rule limits the appeal of tobacco products to children by: * Prohibiting billboards within 1,000 feet of schools and playgrounds. Other advertising is restricted to black-and-white text only; this includes all billboards, signs inside and outside of buses, and all advertising in stores. Advertising inside "adult only" facilities like nightclubs can have color and imagery. * Permitting black-and-white text-only advertising in publications with significant youth readership (under 18). Significant youth readership means more than 15 percent or more than 2 million readers under 18; there are no restrictions on print advertising below these thresholds. * Prohibiting sale or giveaways of products like caps or gym bags that carry cigarette or smokeless tobacco product brand names or logos. * Prohibiting brand-name sponsorship of sporting or entertainment events (including teams and entries), but permitting it in the corporate name. These provisions will be phased in between six months and two years from the date of publication in the Federal Register to give businesses adequate time to comply. ------------------------------------------------------------------------ Final Rule Summary * minimum age of 18 to buy tobacco products * ban vending machines and self-service displays, except in certain nightclubs and other "adult only" facilities totally inaccessible to persons under 18 * ban "kiddie" packs, "loosies," or free samples * mail-order sales permitted * Ban billboards within 1,000 feet of schools and playgrounds. * Other billboards and outdoor and in-store advertising limited to black-and-white text-only, except color, imagery permitted in "adult only" facilities if not visible from outside and not removable. * Advertising in publications with significant youth readership (more than 15 percent or 2 million) limited to black-and-white text only. * Ban brand-name sponsorship of sporting or other events, including cars and teams; only corporate name sponsorship permitted. * Ban brand names on hats, t-shirts, gym bags, etc. ------------------------------------------------------------------------ Legal Issues Relating to FDA Rule On Children and Tobacco FDA Jurisdiction FDA has concluded that cigarettes and smokeless tobacco are delivery devices for nicotine, a drug that causes addiction and other significant pharmacological effects. The Federal Food, Drug, and Cosmetic Act provides that a product is a drug or device if it is an article (other than food) "intended to affect the structure or any function of the body." Nicotine in cigarettes and smokeless tobacco does "affect the structure or any function of the body" because nicotine in these products: * causes and sustains addiction * causes other mood-altering effects, including tranquilization and stimulation * controls body weight. Manufacturers of cigarettes and smokeless tobacco "intend" these effects because: * The addictive and pharmacological effects are so widely known and accepted, a reasonable manufacturer can foresee the products will be used by consumers for these effects. * Consumers use these products predominantly for pharmacological purposes. * Manufacturers know that nicotine in their products causes pharmacological effects and that consumers use their products primarily to obtain these effects. * Manufacturers of these products design the products to provide consumers with a pharmacologically active dose of nicotine. * An inevitable consequence of the design of these products to provide consumers with a pharmacologically active dose of nicotine is to sustain consumers' addiction to nicotine. Rule Protects Appropriate Commercial Speech The U.S. Supreme Court has upheld restrictions on commercial speech if certain standards are met. Given that selling cigarettes and smokeless tobacco to children under 18 is already illegal in every state, the rule is aimed at regulating commercial speech to ensure that an illegal activity is not promoted. Furthermore, the rule is narrowly tailored to meet the tests established by the U.S. Supreme Court in its opinions on commercial speech, including 44 Liquormart, Inc. v. Rhode Island. * Protecting the health of children under 18 is a substantial government interest justifying restrictions on tobacco advertising that appeals to children. * Advertising and promotion have been shown to play a material role in children beginning and continuing to use tobacco products, and therefore the regulations directly advance the government's interest. * Permitting unrestricted advertising in publications primarily read by adults and permitting companies to sponsor events in the corporate name--instead the brand identifications so appealing to young people--are examples of how the rule is narrowly tailored to advance the government's interest. ------------------------------------------------------------------------ New Devices Aim at Improving Pap Test Accuracy by Margie Patlak She had gotten Pap tests each year that were reported as being negative with no abnormal cervical cells noted. But when the 38-year-old woman bled vaginally following sexual intercourse, she returned to her gynecologist and was surprised and dismayed to discover she had an advanced form of cervical cancer. She died just two years later. When her previous Pap tests were reexamined, it was discovered that cancerous cells had not been identified in tests up to two years before she was diagnosed with cervical cancer. This case, though not common, is not unique. Studies done at various Pap screening laboratories in this country show that between 5 and 50 percent of all Pap tests with cancerous cells are inaccurately determined to be free of abnormalities, giving what is known as "false negative" results. Such errors can spell the difference between life and death for some women, because when detected in its early stages nearly all cervical cancers can be cured with minor surgery or other procedures. In contrast, fewer than 20 percent of women with advanced cervical cancer survive more than five years, even with treatment, according to the National Cancer Institute. There are nearly 5,000 deaths due to cervical cancer each year in this country. Recent data from NCI reveal that the number of cases of cervical cancer in white women under the age of 50 in the United States has been increasing 3 percent each year since 1986. In contrast, incidence rates are declining in black women of all ages and in white women over age 50. According to the World Health Organization, cervical cancer is also the most common cancer among women in developing countries. To help improve accuracy, FDA has recently approved two new computer systems for rescreening Pap tests. A Silent Cancer Unlike many cancers that cause pain, noticeable lumps, or other early symptoms, cervical cancer has no telltale symptoms until it is so advanced that it is usually unresponsive to treatment. Symptoms may even be absent at that point, although they often include abnormal vaginal bleeding, such as following intercourse or douching, between menstrual periods, or after menopause. Only in its late stages does cervical cancer cause pain in the lower abdominal or back regions. But because the cervix, which essentially is the mouth of the uterus, can be easily accessed through the vagina, doctors can test for cervical cancer as well as for precancerous changes in the cervix. Most cervical cancers grow slowly over several years and often are preceded by abnormal cells. Cervical cancer can often be prevented with the removal of these cells that are precursors to cancer. (See accompanying article.) To detect abnormal or cancerous cervical cells, George Papanicolaou, M.D., Ph.D., of Cornell University developed in the 1940s what is known today as the Pap test. In this test, a sample of cells is taken from in and around the cervix with a wooden scraper, cotton swab, or small cervical brush. The specimen is smeared on a glass slide, preserved with alcohol, and then sent to a laboratory. There cytotechnologists, specially trained in identifying defective cells, scrutinize the cervical cells under the microscope for any abnormal features associated with cancerous or precancerous cervical cells. These features include dark or irregularly shaped cell nuclei, or small or deformed cells. The Pap test became a routine part of gynecological exams. As a result, there was a 70 percent drop in the number of women dying from cervical cancer between 1950 and 1970, according to NCI. But the problem of errors remained. Such errors are understandable when considering the magnitude of the task set before the cytotechnologist examining Pap slides. These standard-sized laboratory slides are lined with between 50,000 to 300,000 cervical cells. Lurking in these cells may be as few as a dozen abnormal cells. Finding such telltale cells is akin to finding a needle in a haystack, especially at the end of the day when cytotechnologists are likely to have examined nearly 100 Pap slides. In addition, abnormalities in cell shape may be slight and difficult for even the trained eye to detect, or may be masked by infection. Computerized Rescreening The two new systems approved by FDA show promise of substantially improving the accuracy of Pap tests. The computers scan the images for abnormal-looking cells. One system, called PAPNET, uses neural net computer technology, which its manufacturer claims was originally created to detect flying missiles in what is known as the "Star Wars" defense strategy. PAPNET detects abnormal cervical cells with a computer system that essentially has learned by example. This system was created by feeding a series of digitized images of Pap slides to a computer. From these examples, the computer developed the guidelines for predicting abnormal cells. PAPNET scans each Pap slide cytotechnologists have classified as normal and chooses the 128 cells or cell clusters that are most likely to be abnormal. Enlarged color images of these cells are then returned to the cytotechnologist for review. Studies have used PAPNET rescreening to reexamine previous negative Pap smears taken from women with high-grade cervical cell abnormalities or cervical cancers. These studies found that in about one-third of these women, PAPNET testing detected abnormalities missed by manual screening on previous Pap smears. The other Pap test rescreening system is called AutoPap 300 QC. This computerized system uses image processing and pattern recognition techniques to classify cells as abnormal. Hundreds of features--such as size, shape, density, and texture--are considered for each cell. Sophisticated statistical screens use this visual information to predict which cervical cells are abnormal. Following routine screening by a cytotechnologist, all "normal" slides are rescreened by AutoPap 300 QC, which selects 10 to 20 percent of slides with the highest probability of having abnormal cells. These are then rescreened manually by the cytotechnologist. In one study, cytotechnologists randomly rescreening 10 percent of more than 4,000 Pap slides they originally classified as normal detected only about 1 of every 10 false negatives present. Cytotechnologists using AutoPap 300 QC to rescreen the 10 percent of slides the system deemed as being most abnormal detected up to half of all the missed abnormals. Both PAPNET and AutoPap 300 QC can be used by laboratories, and women can ask if the laboratories their Pap smears are sent to employ these rescreening systems. But some labs may not yet be fully familiar with the Pap rescreening systems. "Laboratories are starting to evaluate these devices and determine if and how they will use them," said Louise Magruder, of FDA's division of clinical laboratory devices. Although use of PAPNET and AutoPap 300 QC will considerably decrease the likelihood of missing a diagnosis of cervical cancer, neither system is perfect. Even if they could detect every abnormal cell on a Pap slide, some women with cervical cancer would still be told their Pap tests were normal because there were too few cells on the slide or the cell samples were not taken from both the inside and surface of the cervix. Douching or using vaginal spermicides or medicines a day or two before a Pap test can also wash away abnormal cells and thus reduce the test's accuracy. Also, there is a tiny percentage of women who develop a rare form of aggressive cervical cancer that can develop to an advanced stage in less than a year. In addition, cervical cancer will continue to occur in women who don't receive regular gynecological exams and Pap tests. NCI recommends that all women who are or have been sexually active or have reached age 18 have a Pap smear and gynecological exam as frequently as each year, but at least every three years, depending on their risk factors for cervical cancer. Risk Factors Evidence collected over the past few decades suggests several risk factors for developing cervical cancer. These include having sexual intercourse before age 18, having several sexual partners, or having a sexual partner who was previously married to a woman who had cervical cancer. Scientists are closely scrutinizing the sexually transmitted human papillomaviruses (HPVs), some of which cause genital warts. Research strongly suggests some types of HPVs (there are more than 60 different types) can trigger the growth of abnormal cells in the cervix and are likely to play a key role in the development of cervical cancer. Women who have HPV or whose partners have HPV have a boosted risk of developing cervical cancer. However, many women infected with HPV do not develop cervical cancer, and not all women with cervical cancer harbor HPV. This suggests other factors act with HPV to cause cervical cancer. The genital herpes virus may play a role, as may the strength of a woman's immune system. Women infected with HIV, the virus that causes AIDS, are more likely to develop cervical cancer, as are female organ transplant patients who receive drugs that suppress the immune system to prevent rejection of the new organ. Hormones may also influence the development of cervical cancer. The labeling of oral contraceptives states that some studies have found an increased incidence of cervical cancer in women taking birth control pills, but that this may be related to factors other than the pill. Women whose mothers took the estrogen-like drug diethylstilbestrol (DES) during pregnancy to prevent miscarriage are also more likely to develop cervical cancer. (DES was used to prevent miscarriages from about 1940 to 1970.) Smoking also elevates the risk of cervical cancer, which rises with the number of cigarettes a woman smokes each day and with the number of years she has smoked. Women exposed to other people's tobacco smoke are also more likely to develop cervical cancer. Research suggests women can reduce their risk of cervical cancer by using barrier methods of contraception, such as the diaphragm with spermicide and condoms, probably because such methods decrease the risk of being infected by a sexually transmitted disease. At present, early detection of precancerous tissue remains the most effective way of preventing cervical cancer. With PAPNET and AutoPap 300 QC, that pathway has just become a more reliable route for maintaining good cervical health. Margie Patlak is a writer in Elkins Park, Pa. ------------------------------------------------------------------------ Slow Development Gives Time for Treatment Most cervical cancers gradually progress over a period of years without immediately invading nearby tissue. Yet they leave telltale signposts along their way. Even the transition from a normal to a cancerous cervical cell is usually a gradual one, with several steps that can be seen with the aid of a microscope. In what is thought to be one of the first steps in the development of cervical cancer, the nuclei of cervical cells enlarge and darken. A patch of these abnormal cells is termed a squamous intraepithelial lesion (SIL) because the abnormal cells are present only in the squamous epithelial cells which line the surface of the cervix. SILs are further classified as low-grade if the abnormal cells are of normal size, or high-grade if the cells are smaller than normal. Low-grade SILs are common; most spontaneously revert to normal. But because some will progress to high-grade SILs and then to cervical cancer, most doctors ask women with this Pap diagnosis to have Pap tests every four to six months for about two years. After three consecutive Pap tests come back negative, women can return to a routine screening protocol. If repeated Pap tests show persistent abnormalities, however, a woman's doctor may want to confirm the low-grade SIL diagnosis by further scrutinizing the cervix with other procedures. Colposcopy is a widely used method to check the cervix for abnormal areas. The doctor applies special stains to the cervix and then uses an instrument much like a microscope (called a colposcope) to detect abnormal cells, which turn a different color than healthy cells. The doctor also may want to remove a small amount of cervical tissue for examination with a biopsy. It also may be necessary to scrape more tissue from inside the cervical opening. These procedures can be done in the doctor's office under local anesthesia. If the low-grade SIL diagnosis is confirmed, a doctor may ask the patient to continue to have frequent Pap tests. Alternatively, the doctor may prefer to destroy the abnormal area by freezing it (cryosurgery), burning it (cauterization), or by removing it with a laser or electrosurgical device. Such treatment may cause cramping or other pain, bleeding, or a watery discharge. High-grade SILs rarely regress spontaneously. Most progress to cervical cancer over a period of 10 to 15 years, according to the National Cancer Institute. Women who have high-grade SIL Pap reports usually are asked to undergo a colposcopy or biopsy procedure to confirm diagnosis. Once the high-grade SIL diagnosis is certain, doctors usually destroy the lesion with one of the procedures described in the previous paragraph. Or, the lesion and adjacent tissue may be surgically removed. If a high-grade SIL progresses to the point that the cell nuclei become jagged or irregular in shape, extremely dark, and enlarged, and the cells themselves are strangely shaped (tadpole- or spindle-shaped, for example, instead of round), the lesion is considered cancerous. If the cancer is limited in scope, it may be treated with some of the same methods used to destroy precancerous lesions. For more widespread cancers, more involved surgery is usually done, removing a larger portion of the cervix or the entire uterus, ovaries or fallopian tubes. Depending on the size and location of the tumor, radiation therapy or chemotherapy may also be necessary. --M.P. ------------------------------------------------------------------------ Colds and Flu: Time Only Sure Cure by Tamar Nordenberg It's not chicken soup. Believe it or not, a much more unorthodox therapy of warm-and-cold showers has recently been proposed--though not proven--for the prevention of the common cold. Shower therapy joins an ever-growing spectrum of suggested preventers and treatments for the common cold--among them, hand washing, vitamin C, interferon, seclusion, and various over-the-counter cough and cold medications. "An efficient, practical and inexpensive prophylaxis [preventive measure] against one of the most frequent (and 'expensive') diseases has been identified at last," claims water therapy researcher Edzard Ernst, M.D., in the April 1990 issue of Physiotherapy. Though some may doubt his shower theory, Ernst is right about one thing--the common cold is a frequent and expensive disease, striking some people as many as 12 times a year and leading to some 15 million days lost from work annually in the United States. Influenza, or flu, likewise, is a frequent and expensive disease, reaching epidemic levels in the United States each year. Identify the Enemy Flu is like the cold in many ways--most basically, they're both respiratory infections caused by viruses. If a cold is misdiagnosed as flu, there's no problem. At worst, a cold can occasionally lead to secondary bacterial infections of the middle ear or sinuses, which can be treated with antibiotics. But if the flu is misdiagnosed as a bad cold, potentially life-threatening flu complications like pneumonia may be overlooked. Some of the symptoms of a cold and flu are similar, but the two diseases can usually be distinguished. (See accompanying chart.) Typically, colds begin slowly, two to three days after infection with the virus. The first symptoms are usually a scratchy, sore throat, followed by sneezing and a runny nose. Temperature is usually normal or only slightly elevated. A mild cough can develop several days later. Symptoms tend to be worse in infants and young children, who sometimes run temperatures of up to 102 degrees Fahrenheit (39 degrees Celsius). Cold symptoms usually last from two days to a week. Signs of the flu include sudden onset with a headache, dry cough, and chills. The symptoms quickly become more severe than those of a cold. The flu sufferer often experiences a "knocked-off-your-feet" feeling, with muscle aches in the back and legs. Fever of up to 104 degrees Fahrenheit (40 degrees Celsius) is common. The fever typically begins to subside on the second or third day, and then respiratory symptoms like nasal congestion and sore throat appear. Fatigue and weakness may continue for days or even weeks. "The lethargy, achiness and fever are side effects of the body doing its job of trying to fight off the infection," according to Dominick Iacuzio, Ph.D., influenza program officer with the National Institutes of Health (NIH). Influenza rarely causes stomach upset. What is popularly called "stomach flu"--with symptoms like nausea, diarrhea and vomiting--is technically another malady: gastroenteritis. Cold and flu-like symptoms can sometimes mimic more serious illnesses like strep throat, measles, and chickenpox. Allergies, too, can resemble colds with their runny noses, sneezing, and general miserable feeling. If symptoms persist, become severe or localized in the throat, stomach or lungs, or if other symptoms such as vomiting and behavioral changes occur, consult your physician. "With the typical symptoms, it's not necessary to contact your physician immediately," Iacuzio says. The Treatment Arsenal There is no proven cure for colds or flu but time. However, over-the-counter medications are available to relieve the symptoms. "OTC cough-cold products can make you more comfortable while you suffer," says Debbie Lumpkins, a scientist with the Food and Drug Administration's division of over-the-counter drug products. "They are intended to treat the symptoms of minor conditions, not to treat the underlying illness." Don't bother taking antibiotics to treat your flu or cold; antibiotics do not kill viruses, and they should be used only for bacterial complications such as sinus or ear infections. Overuse of antibiotics has become a very serious problem, leading to a resistance in disease-causing bacteria that may render antibiotics ineffective for certain conditions. Children and teenagers with symptoms of flu or chickenpox should not take aspirin or products containing aspirin or other salicylates. Use of these products in young flu and chickenpox sufferers has been associated with Reye syndrome, a rare condition that can be fatal. Because cold symptoms can be similar to those of the flu, it's best not to give aspirin to people under 20 with these types of symptoms. The active ingredients FDA considers safe and effective for relieving certain symptoms of colds or flu fall into the following categories: * Nasal decongestantsopen up the nasal passages. They can be applied topically, in the form of sprays or drops, or taken orally. But using sprays or drops longer than three days may cause nasal congestion to worsen. * Antitussives, also known as cough suppressants, can quiet coughs due to minor throat irritations. They include drugs taken orally, as well as topical medications like throat lozenges and ointments to be rubbed on the chest or used in a vaporizer. * Expectorants, taken orally, help loosen mucus and make coughs more productive. The effectiveness against cold symptoms of another category of over-the-counter drugs called "antihistamines" is being studied. Currently, OTC antihistamines are approved only for use by sufferers of hay fever and some other allergies. Most nonprescription cough-cold remedies contain a combination of ingredients to attack multiple symptoms. These combination products often contain antipyretics to reduce fever and analgesics to relieve minor aches, pains and headaches. Users of OTC medicines should carefully follow the labeling instructions and warnings. To help people understand the OTC labels, FDA is working with industry on new labeling that would use more consumer-friendly language and standardize the placement of important information from product to product. The Cold War OTC cough and cold medication sales totaled 3.2 billion dollars in 1995, according to a national industry survey. That's no surprise, considering Americans endure about 1 billion colds each year. Children get the most colds--six or eight a year. By contrast, adults average two to four a year, with a greater frequency in the parents of children. The high rate in children is blamed on their lack of a built-up resistance to infection and the close contacts with other kids in schools and day care. Women's closer contact with children may also explain the greater prevalence of colds in women than in men. Adults over 60 usually suffer less than one cold a year, probably because they have built up a natural immunity. Most colds strike Americans in the fall and winter. Contrary to what many people believe, the increased rate of colds during this time is actually not due to the cold weather. So why do more people feel "under the weather" during the winter months? Probably, say researchers at NIH's National Institute of Allergy and Infectious Diseases, because of the greater time spent indoors in cold weather, increasing the opportunity for viruses to spread among people. Also, the lower humidity during the colder months helps cold-causing viruses to thrive and may dry the lining of the nasal passages, making them more susceptible to infection. Because the symptoms of the common cold are caused by more than 200 different viruses--most by the so-called "rhinoviruses" (from the Greek rhin, meaning "nose")--the development of a vaccine isn't feasible. To minimize the spread of colds, people should try to keep their defenses up and their exposure down. First Line of Defense Cold viruses can be transmitted in one of two ways: by touching respiratory secretions on a person's skin (when shaking hands, for example) or on environmental surfaces (like doorknobs or handrails) and then touching the eyes, nose or mouth, or by inhaling infectious particles in the air (like respiratory secretions from a cough or sneeze). The best way to break the chain of infection? Hand washing is the key, according to Iacuzio, along with not touching the nose, eyes or mouth. "Your mucus membranes are your first line of defense against infection," according to Iacuzio. "Interference with the constant passage of mucus raises the chances for entry of the virus." That's why drinking liquids and maintaining a humid environment with a vaporizer may lower susceptibility. To minimize the spread, other helpful measures include avoiding close, prolonged exposure to people with colds, and always sneezing or coughing into a facial tissue and immediately throwing it away. Cleaning environmental surfaces with a virus-killing disinfectant is also recommended. The Flu Fighters Flu typically affects 20 to 50 percent of the U.S. population each winter. It's a highly contagious disease, spreading mostly by direct person-to-person contact. "With the flu, coughing--even more than sneezing--is the most effective method of transmission," Iacuzio says. The flu virus can linger in the air for as long as three hours. In close quarters, conditions are ripe for the spread of the virus. That explains why the highest incidence of the flu is in 5- to 14-year-olds, who spend much of their time in school, in close contact with their classmates. The most serious complications occur in older adults, however. Years ago, there were no practical tools to protect people from flu. In 1918-1919, a global flu epidemic, or pandemic, struck half the world's population and claimed the lives of 20 million. Still today, 10,000 to 20,000 Americans--almost all of them elderly, newborns, or chronically ill--die each year from flu complications, usually pneumonia. The challenge for scientists trying to protect us from the disease is that influenza viruses can change themselves, or mutate, to become different viruses. Scientists have classified flu viruses as types A, B and C. Type A is the most common and leads to the most serious epidemics. Type B can cause epidemics, but usually produces a milder disease than type A. Type C viruses have never been associated with a large epidemic. Vaccine a Powerful Weapon The most important tool for fighting the everchanging flu virus is immunization by a killed virus vaccine licensed by FDA. The vaccine is made from highly purified, egg-grown viruses that have been made noninfectious. Vaccination is available to anyone who wants to reduce their chances of getting the flu. Studies have shown the vaccine's effectiveness rate to be 70 to 90 percent in healthy young adults. In the elderly and in people with certain chronic illnesses, the vaccine sometimes doesn't prevent illness altogether, but it does reduce its severity and the risk of complications. The government's Advisory Committee on Immunization Practices strongly recommends vaccination for the following high-risk groups: * people aged 65 or older * residents of nursing homes and other facilities that provide care for chronically ill persons * people over the age of 6 months, including pregnant women, who have certain underlying medical conditions that required hospitalization or regular doctors' visits during the preceding year. These conditions include: * asthma, anemia, metabolic disease such as diabetes, or heart, lung or kidney disease * impaired immune system due to HIV infection, treatment with drugs such as long-term steroids, or cancer treatment with radiation or chemotherapy * children and teenagers (6 months to 18 years) who must take aspirin regularly and therefore may be at risk of developing Reye syndrome if they get the flu. To reduce the risk of transmitting flu to high-risk persons--and to protect themselves from infection--the advisory committee recommends flu shots for people with regular close contact with high-risk groups. Such people include health-care workers, nursing home personnel, home-care providers, and children. Police, firefighters, and other community service providers may also find vaccination useful. Because it takes the immune system about six to eight weeks to respond to vaccination, the best time to get the flu vaccine is mid-October to mid-November, before the December-to-March U.S. flu season hits. The vaccine's most common side effect is soreness at the vaccination site for up to two days. Some people may experience post-shot fever, malaise, sore muscles, and other symptoms resembling the flu that can last for one to two days. Actually, the flu vaccine can't cause flu because it contains only inactivated viruses. Some people--but not many--should avoid the flu shot. People allergic to eggs and people with certain other allergies and medical problems like bronchitis or pneumonia should consult a doctor before getting a flu shot. And those with a high fever should not receive the vaccine until they feel better. Pregnant women who have a high-risk condition should be immunized regardless of the stage of pregnancy; healthy pregnant women may also want to consult their health-care providers about being vaccinated. In the rare cases when the vaccine is not advisable, two prescription drugs are available for flu prevention: Symmetrel (amantadine), approved by FDA in 1976, and Flumadine (rimantadine), approved by FDA in 1993. Either drug also can be used to reduce symptoms and shorten the illness if administered within 48 hours after symptoms appear. Individuals opting for the vaccine should be immunized annually, since the immunity is believed to last only about a year, and because the vaccine's composition changes each year based on the flu strains scientists expect to be most common. To decide which strains of influenza virus should be incorporated into the vaccine for the coming flu season, FDA's Vaccines and Related Biologicals Advisory Committee meets in late January each year to consider reports from national and international surveillance systems. A World Health Organization panel meets in Geneva in mid-February to make final recommendations for the next season's flu vaccine. The strains are labeled by their type (A, B or C) and the place where the strain was isolated. In 1996, the predominant strains were A/Johannesberg, A/Texas, and B/Beijing. The anticipated strains for the 1996-1997 flu season are largely the same: A/Texas, A/Wuhan-like, and B/Beijing. "In the not-too-distant future," says Iacuzio, "consumers may have alternatives to the flu shot, including different delivery methods like nasal drops or a spray." Major pharmaceutical companies, in cooperation with scientists representing NIH, FDA's Center for Biologics Evaluation and Research, and academia, are making significant strides, also, toward an even more protective vaccine. First Do No Harm If, despite precautions, you do get a cold or flu, besides taking an OTC medication if needed and as directed, drink fluids and get plenty of bed rest. "Your body is trying to attack the virus," Iacuzio says. "Give in, and give your body a chance to fight off the infection. It takes energy to do that." Many people are convinced that vitamin C can prevent colds or relieve symptoms. There is no conclusive evidence of this, but the vitamin may reduce the severity or duration of symptoms, according to the National Institute of Allergy and Infectious Diseases. But taking vitamin C in large amounts over long periods can be harmful, sometimes causing diarrhea and distorting common medical tests of the urine and blood. Another proposed therapy, interferon-alpha nasal spray, can prevent infection and illness but causes unacceptable side effects like nosebleeds, according to the institute. Many patients have their own, unproven theories about what works. "As long as it's not harmful, why not try it?" says Iacuzio. "But be skeptical of something that hasn't been clinically proven in a well-designed, placebo-controlled study." So what about chicken soup? It may soothe a sore throat, unstuff clogged passageways, and hydrate a thirsty body. At the very least, according to Iacuzio, "It's good TLC. Psychologically, that's important when you're sick." Tamar Nordenberg is a staff writer for FDA Consumer. ------------------------------------------------------------------------ Is It a Cold or the Flu? Symptoms Cold Flu fever rare characteristic, high (102-104F); lasts 3-4 days headache rare prominent general aches,pains slight usual; often severe fatigue,weakness quite mild can last up to 2-3 weeks extreme exhaustion never early and prominent stuffy nose common sometimes sneezing usual sometimes sore throat common sometimes chest discomfort, mild to moderate common;can become severe cough hacking cough ------------------------------------------------------------------------ Help for People with Paget's Disease by Paula Kurtzweil Something weighs heavily on Jan Brown's head every day. Something called Paget's disease of bone, and it affects her skull. She feels the effects constantly, like 5 pounds of pressure, she says. "It's always there," the 57-year-old Rockville, Md., woman says. "I can feel it right now as I speak." Sometimes she takes Tylenol (acetaminophen) for the pain. Seventy-two-year-old Kenneth Halstead, of Raleigh, N.C., also has Paget's disease. It affects his skull, as well as his spine, hips, pelvis, and right leg. It's evident from his right leg, which is bowed. On his right foot, he wears a "built-up" shoe to compensate for the half an inch his leg has shrunk. He also wears a hearing aid. A 78-year-old woman from Washington, D.C., who asked that her name not be used, also has the disease. She, too, wears a hearing aid, and her head is pushed forward and down, preventing her from tilting her head back to look up. Paget's disease is the second most common bone disease in the United States. Osteoporosis is No. 1. Paget's disease can cause pain, deformities, hearing loss, and limits on activity. The disease, which affects people in different ways, also can cause arthritis and other serious consequences. Many people may dismiss these disabilities as a natural part of aging. The average age of diagnosis is 58 (although the disease actually may begin much earlier). But the disease is treatable, and with newer drugs on the market--including two approved by the Food and Drug Administration in 1991 and 1995--there is greater opportunity for patients with Paget's disease to find pain relief, limit the progression of their disease, and, in some cases, reverse bone damage. The challenge now, experts say, is to identify patients early and, if feasible, start treatment promptly. It's estimated that 3 percent of the American population over 40 is affected. The problem is that many people with Paget's disease don't know they have it because often it develops without symptoms. Bone Gone Awry Paget's disease gets its name from Sir James Paget, an English doctor who served as surgeon to Queen Victoria. He first described the disease's characteristics in 1876. Many years later, scientists realized Paget's disease is a disruption in the normal activity of bone tissue. Bone is constantly being broken down by cells called osteoclasts and rebuilt by cells called osteoblasts. This is called bone turnover, and throughout the entire skeleton, this process is normally in precise balance. In Paget's disease, the process goes awry. In discrete portions of bone, overly large osteoclasts dissolve bone too quickly--as much as 50 times faster than normal. Osteoblasts try to compensate for the increased pace by rapidly depositing new bone. But, in the hurried process, the newly deposited bone is loose and bulky in structure, rather than strong, compact, and neatly arranged. Over time, pagetic bone becomes weak and soft and can easily bend, actually shortening the part of the body affected: for example, a leg or the spine. The bone may enlarge in diameter, though, and it can become painful and break easily. Any bone can be affected, but the most common sites are the spine, skull, pelvis, and legs. Some patients may have only one affected bone, while others may have two or more. The disease usually does not spread to unaffected bones. Common deformities include bowed legs, an enlarged head or pelvis, and a curved back. Pagetic bone can affect other parts of the body, causing added problems. For example, it can change bones around joints, causing arthritis. If in the skull and the temporal bone (the bone surrounding the inner ear), Paget's disease can affect hearing. When it affects the facial bones, it can cause dental problems. Because of changes to the bone, pagetic bones often contain more blood vessels than normal, increasing blood flow to affected bones. Because the heart has to work harder to pump the extra blood, Paget's patients with heart disease may be at even greater risk for heart failure. Paget's disease is rarely fatal. However, fewer than 1 percent of patients may develop osteosarcoma, a form of bone cancer, and other sarcomas. Most Paget's patients die from causes unrelated to Paget's disease. Causes No one knows what causes Paget's disease, although genetics may play a role. Several studies indicate that 15 to 30 percent of Paget's patients have family members with the disease. Those with a first-degree relative--parent, sibling or child--with Paget's disease are seven times more likely to develop the disease than those without an affected first-degree relative. "It clearly runs in families," says Ethel Siris, M.D., an endocrinologist at Columbia University College of Physicians and Surgeons in New York City. She says the risk increases if the first-degree relative has more severe disease and an early age at diagnosis. Paget's disease is rarely diagnosed in people under 40, although there have been cases. Siris says she's treated patients in their late 20s and early 30s. The family history related by several patients seems to bear out Siris' conclusions: Evelyn Nef, 83, of Washington, D.C., who was diagnosed with Paget's disease in 1962, says her brother and sister also suffer from the disease. Halstead, who was diagnosed in his 30s, says his two brothers have the disease and his mother, who is 102, was diagnosed three years ago. The role of genetics also is supported by observations that certain ethnic groups have higher rates of Paget's disease. According to the Paget Foundation, Paget's disease is most common in Caucasian people of Anglo-Saxon and European descent, but it also occurs in African Americans. It is rare in people of Asian descent. Research by Frederick Singer, M.D., an endocrinologist with the John Wayne Cancer Institute at Saint John's Hospital and Health Center in Santa Monica, Calif., may eventually yield proof of a genetic role. Studying an Iowa family with a history of Paget's disease, Singer and his colleagues traced a genetic abnormality to chromosome 18. The precise gene has yet to be identified, Singer says, but when it is, genetic tests may be able to predict who will get the disease. "I think that's coming pretty fast," he says. Many experts, Singer included, also suspect that a slow virus may play a role. The theory is that the virus infects a person early in life, without causing symptoms for many years. This theory is based on studies identifying viral-like particles in osteoclasts from pagetic bone. According to Sakamuri Reddy, Ph.D., assistant professor at the University of Texas Health Science Center at San Antonio, these particles react with antibodies that detect a group of viruses which includes the measles and canine distemper viruses. Reddy and his group also have shown that osteoclasts from patients with Paget's disease contain the measles virus messenger RNA. Osteoclasts of people without Paget's disease do not contain this RNA. This isn't to say that measles is the cause, though, says Leo Lutwak, M.D., Ph.D., an endocrinologist and medical reviewer in FDA's division of metabolism and endocrine drug products. "The agent may be related to the measles virus," he says. How do the viral theory and genetics' role fit together? Experts in Paget's disease surmise that heredity may put people at risk for the suspected Paget's virus. "It may be that some people inherit the tendency to have this virus affect their osteoclasts, while other people are, due to their own genetic makeup, more resistant," Siris writes in the Paget Foundation publication A Patient's Guide to Paget's Disease of Bone. Accidental Diagnoses Many patients, especially those with mild cases, first learn they have Paget's disease when a routine blood test reveals an abnormally high blood level of total alkaline phosphatase, an enzyme produced by osteoblasts, as well as cells of the intestine and liver. When osteoblasts are more numerous or are especially active, the amount of alkaline phosphatase throughout the skeleton is increased. The increased bone alkaline phosphatase spills over into the blood, increasing the serum alkaline phosphatase. A normal serum alkaline phosphatase ranges from 20 to 141 units per liter (U/L). Patients with severe Paget's disease may have six to 10 times that range. Halstead recalls that at one point his serum alkaline phosphatase rose to nearly 2,000 U/L. Jan Brown of Rockville recalls her alkaline phosphatase was more than 1,000 U/L when she was first diagnosed. "The doctor said he had never seen such a high alkaline phosphatase in as young a person," recalls Brown, who was 52 when diagnosed with Paget's disease. Sometimes, Paget's patients first learn about their diagnosis when an x-ray taken for other reasons reveals pagetic bone. Usually, bone pain is the first complaint of patients with symptoms. Bone deformities, arthritic pain, and hearing loss are other complaints that may lead patients to seek medical attention. Laboratory tests, such as the serum alkaline phosphatase and urinary hydroxyproline (a measure of bone breakdown), may offer evidence of Paget's disease, but x-rays give the definitive diagnosis. Bone scans also may be taken to determine the extent and activity of Paget's disease. Bone scans involve less radiation and are more sensitive than x-rays in detecting areas of pagetic bone. Treatments Safe drugs for treating Paget's disease of bone became available only in the last 25 years. FDA approved the first two, calcitonin and Didronel (etidronate disodium), in the mid-1970s. Salmon calcitonin (Calcimar and Miacalcin) and human calcitonin (Cibacalcin) are synthetic substances similar to the human hormone calcitonin. Synthetic calcitonin preparations help inhibit bone breakdown by decreasing the activity of osteoclasts. Only injectable calcitonin is approved for patients with Paget's disease, although nasal-spray calcitonin, which is approved for other uses, is under study for Paget's disease also, according to the Paget Foundation. Didronel is taken orally in the middle of a four-hour fast. It is a bisphosphonate, a class of drugs that slows bone turnover. Two newer bisphosphonates, Aredia (pamidronate disodium for injection) and Fosamax (alendronate sodium tablets), appear to achieve more effective results--as measured by laboratory tests--according to studies, and usually in smaller doses because they are more potent. Aredia, approved by FDA in October 1991, is given intravenously over four hours daily for three consecutive days. Fosamax, approved by FDA in October 1995, is taken orally. Because this medicine is poorly absorbed, patients should take Fosamax with a glass of water first thing in the morning, then wait at least 30 minutes before taking other medications, eating, or drinking anything other than water. Also, to help prevent esophageal irritation and to ease delivery of the medicine to the stomach, patients should drink a glass of water and not lie down for at least 30 minutes after taking Fosamax. In clinical studies, patients receiving Fosamax had a 20 to 25 percent greater drop in serum alkaline phosphatase levels than those receiving Didronel. The drop was up to 65 percent greater compared with placebo, which had little effect on alkaline phosphatase levels. Bone tissue studies indicated that normal bone was produced during treatment with Fosamax, even where preexisting bone had the abnormally disorganized pattern characteristic of Paget's disease. Fosamax and Didronel usually are taken for no longer than six months at a time. If symptoms worsen or laboratory tests indicate a worsening of the disease, the drugs may be restarted after at least a six-month break from the medications. Additional Therapies According to the Paget Foundation, several more bisphosphonate drugs are undergoing clinical tests. These drugs may offer greater ease of use, says Charlene Waldman, executive director of the Paget Foundation. Because new bone formation occurs as part of the process of repair in pagetic bone, it is important that along with calcitonin and the bisphosphonates to inhibit abnormal bone breakdown, patients eat a diet that provides 1,000 to 1,500 milligrams of calcium and 400 International Units of vitamin D daily. These nutrients are needed for proper bone formation. Calcium can be obtained by eating a well-balanced diet that includes foods that are good sources of calcium--for example, milk and milk products, dark-green leafy vegetables (such as mustard greens and kale), and canned fish with soft bones (such as sardines and salmon). Dietary supplements of calcium may be another source. Some Paget's patients, especially those with severe bowing of legs, fractures, and degenerative arthritis, may need splints, braces, and other devices such as canes and walkers. Patients also may receive physical therapy. Although uncommon, surgery may be required, especially in cases of fractured bones, severe arthritis, and progressive deformity of leg bones. Exercise is important for patients with Paget's disease, just as it is for everyone. Because patients with Paget's disease are prone to bone fractures, they should consult their doctors or physical therapists before starting an exercise program. Various laboratory tests monitor the progression of Paget's disease. The most common is the total alkaline phosphatase. FDA has cleared two tests--Hybritech Ostase in 1994 and Metra Alkphase-B in 1995--that measure only the alkaline phosphatase from bone, since the enzyme in the blood can come from other organs, too. A possible future test, which is still under research, would measure osteocalcin, a byproduct of osteoblasts, to determine bone turnover rates. Deciding When to Treat For many years, doctors generally treated patients with Paget's disease only if they had symptoms. In recent years, with the availability of a wider range of drugs, doctors have begun treating patients without symptoms, as well, hoping that the drugs may prevent the effects of Paget's disease. Factors to consider in deciding whether to treat patients without symptoms, according to Siris, are the location of the disease and the likelihood of its progression. Diseased bone near joints, in the spine or skull, or in the leg bones are particularly "bad spots," she says, and may indicate the need for drug therapy. Patients who are told they have Paget's disease may want to seek a medical specialist in that condition. The Paget Foundation recommends endocrinologists (doctors who specialize in hormonal and metabolic disorders) or rheumatologists (doctors who specialize in joint and muscle disorders). Orthopedic doctors (who specialize in bone problems), neurologists (doctors who specialize in nerve disorders), and otolaryngologists (eye, ear, nose, and throat specialists) also may be called on to evaluate specific symptoms. Siris and Michael McClung, M.D., an endocrinologist and director of the Oregon Osteoporosis Center in the Oregon Health Sciences University in Portland, say that too often doctors who aren't specialists in the disease fail to follow up on laboratory tests or x-rays that indicate Paget's disease. "They might tell patients: 'Forget about it. You'll just end up in a wheelchair,'" Siris says. She believes that many doctors aren't aware of current treatments because effective drugs for Paget's disease weren't available when they were trained. Since Paget's disease often runs in families, medical experts recommend that people with a family history of Paget's disease have their serum alkaline phosphatase measured after age 40, since the disease rarely shows up in people under 40. The laboratory test can be done as part of the routine medical exam. With prompt medical attention and treatment, when needed, people with Paget's disease may be able to avoid some of the disease's serious, often painful effects. Maryland resident Brown hopes that will be true for her. "[The disease] is foremost in my mind," she says. "I wonder: 'Am I going to suffer any deformities from this?' I don't know. But I must be treated or so many things could happen." Paula Kurtzweil is a member of FDA's public affairs staff. ------------------------------------------------------------------------ More Information The Paget Foundation for Paget's Disease of Bone and Related Disorders 200 Varick St., Suite 1004 New York, NY 10014-4810 (1-800) 23-PAGET E-mail:pagetfdn@aol.com World Wide Web: http://www.housecall.com/ Osteoporosis and Related Bone Diseases National Resource Center 1150 17th St., N.W., Suite 500 Washington, DC 20036-4603 (1-800) 624-BONE TTY for hearing-impaired callers: (202) 466-4315 E-mail:orbdnrc@nof.org World Wide Web: http://www.osteo.org/ ------------------------------------------------------------------------ Inside FDA: Office of Women's Health by Isadora B. Stehlin This is one in a series of articles on FDA activities and concerns. When FDA's Office of Women's Health announced that 1995 annual funds were available for agency research projects, Mary Lou Tortorello, a microbiologist with FDA's Center for Food Safety and Applied Nutrition, knew just the project to propose. She wanted to develop a rapid test for Listeria monocytogenes, a microorganism widespread in the environment that may contaminate many types of foods. She thought the test could have a major impact on women's health, since Listeria can cause miscarriages and stillbirths in pregnant women. "By current standard methods, it takes at least four days to detect Listeria in food, and that's only if everything works as it is supposed to," says Tortorello. "A rapid test could really enhance food safety." Tortorello's research is one of more than 50 projects within the agency that have been funded by the Office of Women's Health since it was established in July 1994. The office, with a $2 million annual budget, promotes testing of FDA-regulated products in women, supports research and education to increase knowledge of women's health issues, and forms partnerships with other government agencies and advocacy groups to advance women's health objectives. Women's health issues of particular concern to OWH include: * cardiovascular disease * cancer screening and treatment * sexually transmitted diseases, including HIV * contraception, pregnancy and childbirth * hormone replacement therapy for menopause * osteoporosis and other diseases affecting older women * autoimmune diseases. Central to the office's mission are increasing the number of women in clinical trials and analyzing data for important effects that vary with gender. Historically, women have been neglected in clinical trials for new drugs, devices, and biological products. Attention to remedying this situation was integral to the genesis of the Office of Women's Health and is one of its major issues, explains Audrey Sheppard, acting director of the office. One of the first projects the office funded in 1994 was a study to determine how women newly diagnosed with breast cancer obtained clinical trial information. "There's a great misunderstanding about the National Cancer Institute's Physician Data Query [PDQ] clinical trial database," says Patty Delaney, project coordinator and cancer liaison in FDA's Office of AIDS and Special Health Issues. Not every trial is included, she explains, only trials sponsored by NCI and a few others submitted voluntarily by nongovernment sponsors. "If a manufacturer is conducting one on its own, it is likely not to be in NCI's database." The project, conducted by a contractor for FDA, involved calling more than 100 different telephone numbers that supplied cancer information. Results showed there was no simple, comprehensive way to find out about all the current clinical trials on breast cancer. University medical centers and other research sites often only offered information on studies they were conducting, and when asked where someone could get information on other studies, callers were usually referred to NCI's cancer hot line, (1-800)4-CANCER. Because there is no centralized source for information on all current clinical trials, "patients and their doctors have trouble finding suitable trials, and manufacturers have trouble filling trials," says Marietta Anthony, Ph.D., a microbiologist with the Office of Women's Health. Based on these conclusions, the National Action Plan on Breast Cancer, an organization funded by both private groups and the Department of Health and Human Services, awarded FDA $100,000 to assist NCI in getting drug, biologics and device manufacturers to voluntarily add their breast cancer clinical trials to the PDQ database. The office has also funded research projects and studies to: * Develop a computer model to simulate the potential for a virus to break through a protective barrier such as latex, used in surgical gloves and condoms. * Develop a pilot tracking system to monitor the participation of women in clinical trials. * Examine the effects of the anti-breast cancer drug tamoxifen (marketed as Nolvadex) on the rat uterus. Preliminary studies of women taking tamoxifen, which can delay or prevent relapse in patients who have undergone surgery for breast cancer, have shown that the drug poses an increased risk of cancer of the uterus. * Determine if changes in female sex hormone levels that occur during the menstrual cycle, pregnancy and menopause affect the activities of cytokines (hormone-like proteins that act as communicators between cells). Limited evidence suggests that the cause of systemic lupus erythematosus, an immune-system disease that mainly affects women, may be linked to the interaction of these cells. In addition to funding research, the office has also supported education projects that address women's health issues. One of these efforts, "The Minority Women's Health Empowerment Project," attracted nearly 500 participants. Theresa Holmes, a public affairs specialist with FDA's Philadelphia office, and Joan Lytle, a public affairs specialist with the agency's Newark office, developed the project and six half-day workshops held during the fall of 1995. Four were held in different New Jersey cities, one in Philadelphia, and one in Wilmington, Del. "These workshops provided really practical nuts and bolts information on diseases and conditions, prevention and diagnosis, and remedies," says Sheppard. Some critical health problems of minority women include cervical cancer, which is approximately three times higher among black women than white women; heart disease, which is the leading cause of death in Latino women; and hypertension, stroke, diabetes, lupus, and other chronic diseases, which are responsible for a disproportionate number of deaths in young African-American women. Other education projects funded by the Office of Women's Health include: * Mammography Quality Standards Act brochure for consumers * Mammography Quality Standards Act speakers kit to help FDA and state radiation control personnel explain MQSA requirements, as well as FDA's programs and policies for mammography facility accreditation and inspection * Women of Color Outreach project to expand minority women's involvement in the FDA policy development process * Hispanic Women's Health Conference in Miami on May 9 and 10, 1996 * Asian Pacific Islander Group outreach to encourage use screening tests such as mammograms and pap smears. Asian language translations of FDA educational materials were distributed at health conferences, community activities, and medical centers in California. * Women's Health Internet Initiative to provide information about women's health issues related to food safety, nutrition and cosmetics. Its World Wide Web address is http://vm.cfsan.fda.gov/~dms/wh-toc.html. OWH also coordinates working groups that bring together agency experts. For example, for the working group on older women's issues, "the office is bringing together people throughout the agency who have a piece of the osteoporosis puzzle--the people who approve the drugs, the people who approve the bone measurement devices, and the people who know all about calcium and other foods," explains Sheppard. In partnership with women's organizations, the office is initiating a new public education campaign titled "Women's Health: Take Time to Care." The campaign will target middle-aged and older women, with special emphasis on women who are medically underserved. As the Office of Women's Health continues to define its role, "we really do see ourselves as not just coordinating and educating," says Sheppard, "but also determining where there needs to be advances in thinking, in policy, and in regulation." Isadora B. Stehlin is a member of FDA's public affairs staff. ------------------------------------------------------------------------ Probing the Pancreas by Craig D. Reid, Ph.D. The human pancreas, an elongated, flattened gland behind the stomach, is involved in or affected by a number of diseases, including diabetes mellitus, cystic fibrosis, pancreatitis, and pancreatic cancer. These conditions are diagnosed and treated with products regulated by the Food and Drug Administration. The pancreas is composed of two major types of tissues: * exocrine tissue (acini), which secretes digestive enzymes via the pancreatic duct into the duodenum (part of the small intestine leading from the stomach) * endocrine tissue (islets of Langerhans), which produces and secretes the hormones insulin and glucagon directly into the blood. Endocrine tissue contains alpha, beta and delta cells. Beta cells produce insulin and alpha cells produce glucagon. These hormones regulate blood glucose levels. Delta cells secrete the hormone somatostatin, which inhibits insulin and glucagon secretion. Diabetes A deficiency of insulin in the body results in diabetes mellitus, which affects about 13 million individuals in the United States. It is characterized by a high blood glucose (sugar) level and glucose spilling into the urine due to a deficiency of insulin. As more glucose concentrates in the urine, more water is excreted, resulting in extreme thirst, rapid weight loss, drowsiness, fatigue, and possibly dehydration. Because the cells of the diabetic cannot use glucose for fuel, the body uses stored protein and fat for energy, which leads to a buildup of acid (acidosis) in the blood. If this condition is prolonged, the person can fall into a diabetic coma, characterized by deep labored breathing and fruity-odored breath. There are two types of diabetes. In Type I diabetes, formerly called juvenile-onset diabetes, the pancreas cannot produce insulin. People with Type I diabetes must have daily insulin injections. But they need to avoid taking too much insulin because that can lead to insulin shock, which begins with a mild hunger. This is quickly followed by sweating, shallow breathing, dizziness, palpitations, trembling, and mental confusion. As the blood sugar falls, the body tries to compensate by breaking down fat and protein to make more sugar. Eventually, low blood sugar leads to a decrease in the sugar supply to the brain, resulting in a loss of consciousness. Eating a sugary food can prevent insulin shock until appropriate medical measures can be taken. Type II diabetes, formerly called adult-onset diabetes, can occur at any age. The pancreas can produce insulin, but the cells do not respond to it. For many years, treatment was insulin therapy for Type I and oral sulfonylureas and/or insulin therapy for Type II. Metformin (glucophage) was the first antidiabetic drug approved by FDA (May 1995) for the treatment of Type II diabetes since the oral sulfonylureas were introduced in 1984. Metformin promotes the use of insulin already in the blood. This May 1995 approval was followed by the September 1995 approval of another antidiabetic drug, Acarbose (precose), in September 1995. It slows down the digestion and absorption of complex sugars, which reduces blood sugar levels after meals. Before 1982, insulin was purified from beef or pork pancreas. This was a problem for those diabetics allergic to animal insulin. Researchers produced a synthetic insulin called humulin. Approved by FDA in 1982, it was the first genetically engineered consumer health product manufactured for diabetics. Synthetic insulins can be produced in unlimited quantities. Another possible treatment for diabetes includes surgically replacing the pancreas' endocrine tissues (islets of Langerhans) with healthy islet of Langerhans tissue grafts. Since 1988, 45 patients worldwide have undergone successful transplantation. Cystic Fibrosis The major problem of cystic fibrosis, the number one genetic killer disease of children in the United States, is that the body overproduces thick, sticky mucus. The mucus blocks the pancreatic ducts, which impedes the flow of the pancreatic juices from the pancreas into the duodenum of the small intestines. Food cannot be properly digested. Without treatment, children with cystic fibrosis suffer from malnutrition and constant diarrhea; their average life expectancy is 21. Pancreatic enzyme preparations are usually used to minimize the disease's effects on the pancreas. Pancreatic juices contain enzymes for digesting all three major food types (proteins, carbohydrates and fats), as well as quantities of bicarbonate ions, which play an important role in neutralizing the acid emptied by the stomach into the duodenum. The most important enzyme for fat digestion is pancreatic lipase, which is capable of changing fat into glycerol fatty acids and cholesterol. Hormones regulate pancreatic secretions. Food enters the small intestine. The hormones secretin and cholecystokinin cause the pancreas to create large quantities of fluid containing bicarbonate ions, which neutralizes the acid stomach contents. Pancreatitis Another common disease associated with the exocrine function of the pancreas is pancreatitis (inflammation of the pancreas), which can be either acute or chronic. The most common cause of acute pancreatitis is blockage by a gallstone of the main secretory duct from the pancreas as well as the common bile duct. When this happens, large quantities of pancreatic secretions pool in the pancreas and can digest the entire pancreas within a few hours. But because the islets of Langerhans are not adversely affected, the pancreas can continue secreting insulin. Acute pancreatitis is a condition demanding immediate medical attention. It is characterized by abdominal pain, vomiting, abdominal swelling and gas, fever, muscle aches, and a drop in blood pressure. When appropriately treated, the effects of acute pancreatitis usually calm down within five to seven days. Treatment includes stopping oral consumption and providing nourishment only with intravenous fluids. Chronic pancreatitis occurs when acute pancreatitis continues until pancreatic function is greatly diminished. Symptoms include persistent pain in the upper abdomen which can radiate to the back and last for days or weeks, with mild jaundice (yellow skin and eyes) and rapid weight loss. A person can have recurrent attacks over several years. This may result in secondary bacterial infections of the pancreas, calcium deficiencies, and Type II diabetes. Pancreatic Cancer Pancreatic cancer is the fourth leading cause of cancer deaths in the United States, affecting about 27,000 persons yearly. It is second only to colon cancer as a cause of death from gastrointestinal malignancy. It affects men twice as frequently as women and is more likely to develop after the age of 40. Pancreatic cancer risks increase with chronic pancreatitis, diabetes mellitus, genetic factors (more common in blacks than whites), smoking, excess alcohol consumption, high-fat diets, and exposure to industrial chemicals such as urea, naphthalene or benzidine. Symptoms include weight loss, abdominal pain, nausea, loss of appetite, itching, jaundice, and constipation. Abdominal stress may improve or worsen after eating, and the pain may increase after lying down. Because its symptoms mimic many other common health problems, it often goes undetected until it is too late to treat effectively. When early diagnosis and early treatment are possible, however, survival chances increase. Imaging with endoscopic ultrasound may aid early diagnosis. Researchers are also rapidly building a library of potential genetic markers that indicate the onset of pancreatic cancer. Treatment includes chemotherapeutic drugs and traditional surgical techniques. The most commonly used chemotherapeutic agents are 5-Fluorouracil (5-FU) and the recently approved Gemzar (gemcitabine), a nucleoside analog that mimics DNA building blocks. FDA's approval of Gemzar last May was based on two clinical studies in patients with cancer that was locally advanced or had spread beyond the pancreas. These studies found improvement with Gemzar in what is termed "clinical benefit response"--a measure including changes in patients' use of painkillers, pain intensity, and body weight. The first study, conducted with patients who had never before received chemotherapy, showed that when compared to patients receiving 5-FU therapy, patients treated with Gemzar had a statistically significant improvement in clinical benefit (23.8 percent versus 4.8 percent) and in median survival (5.6 months versus 4.2 months). A second study conducted in 63 patients previously treated with 5-FU therapy and then given Gemzar showed a clinical benefit response of 27 percent and a median survival of 3.8 months. Before its approval, FDA authorized Gemzar's manufacturer, Eli Lilly and Company, to make the drug available through a Treatment IND (investigational new drug) program. More than 2,800 patients received the drug under this program between February 1995 and May 1996. Treatment INDs allow drug developers to give patients access to drugs before they are approved for marketing in cases of immediately life-threatening or otherwise serious diseases. Cryosurgery, a type of surgery in which extremely low temperatures are employed either locally or generally to destroy tissue, is also being investigated for use in pancreatic cancer. The technique involves specific time length and time interval applications by a probe containing liquid nitrogen to freeze the cancer cells to death. The advantages of cryosurgery are that it is inexpensive, requires shorter hospital stays, and causes less blood loss. Pancreatic diseases are among the most common and most deadly diseases that affect Americans today. Due to genetics and the pancreas' inability to cope with disease, having one pancreatic disease primes the body to contract or develop a second pancreatic disease. Although scientists have made considerable progress in the treatment of diabetes, early detection and treatments for cystic fibrosis and pancreatic cancer don't always guarantee the patient will live a long normal life. However, researchers are constantly searching for new and improved methods to complement or replace current therapies in an attempt to at least improve the patient's quality of life. Craig D. Reid, a writer in Los Angeles, was diagnosed with cystic fibrosis more than 30 years ago. ------------------------------------------------------------------------ Updates New Pertussis Vaccine Safer for Infants An acellular vaccine recently licensed by FDA protects infants against pertussis, or "whooping cough," while causing fewer side effects than whole-cell pertussis vaccines. Acellular pertussis vaccines contain only parts of the pertussis bacterium thought to be important for immunity, while whole-cell vaccines contain the whole, killed bacterium. Currently, children in the United States receive a whole-cell pertussis vaccine in combination with diphtheria-tetanus toxoid, or DTP, at 2, 4 and 6 months of age, with additional doses of either a DTP or DT vaccine with an acellular pertussis component (DTaP) between 12 and 18 months and before entering elementary school. The acellular vaccine licensed July 31 for the first three doses is one of two DTaP vaccines already approved for the fourth and fifth doses. Pertussis is a highly communicable respiratory disease that can be especially serious for infants. The coughing and choking that occur make breathing difficult and can last for several weeks. Occasionally, infants can die from the disease. According to the national Centers for Disease Control and Prevention, in 1994 and 1995 a total of approximately 9,500 cases of pertussis were reported in the United States. The World Health Organization reports that pertussis causes approximately 350,000 deaths worldwide. Safety data from a number of studies indicate that the DTaP vaccines cause fewer adverse reactions than DTP vaccines in the first three doses. Reactions can include local redness or swelling, as well as fever, drowsiness, irritability, or prolonged, high-pitched crying. Studies are in progress to help determine the extent of these reactions when children receive the acellular pertussis vaccine for all five doses. Infrequent, serious events such as seizures have been reported after immunizations with both DT P and DTaP. Two clinical studies were conducted to assess the efficacy of the pertussis component of this DTaP vaccine for infants. In these studies, the acellular pertussis vaccine was estimated to be between 69 and 80 percent effective in preventing pertussis, depending on the way the study was designed and completed. (The whole-cell vaccine is about 80 percent effective.) Children who have begun their immunizations with DTP should continue to receive their fourth and fifth doses as DTaP. For those children who will now receive DTaP at 2, 4 and 6 months, a fourth dose of DTaP is recommended in the second year of life. Studies are being planned to help determine recommendations for the fifth dose. The acellular pertussis component of the vaccine is produced by the Research Foundation for Microbial Diseases of Osaka University in Japan. It is combined with diphtheria and tetanus toxoids by Connaught Laboratories, Inc., Swiftwater, Pa., and is sold under the trade name Tripedia. (See also "New Pertussis Vaccine Offers Prevention Alternative," in the September 1992 FDA Consumer.) Nicotine Patches Available OTC Two different nicotine patches to help smokers quit the habit have made the switch. Formerly available by prescription only, the smoking cessation aids have been approved by FDA for over-the-counter marketing. The Nicotrol Transdermal System was approved as an OTC drug product for adults last July. The NicoDerm CQ was switched for adult use last August. When used according to directions, the patches deliver a continuous low level of nicotine that helps reduce nicotine craving and other withdrawal symptoms. About 35 million to 45 million U.S. adults are addicted to nicotine due to cigarette smoking. The six-week Nicotrol cessation aid includes an audiotape and other user information. The one-month quit rate among smokers who use the patch and accompanying materials is about 20 percent. Many smokers who use the Nicotrol patch stop smoking for at least a few days but may start smoking again. Most smokers quit several times before they completely stop. The NicoDerm eight-to-ten-week treatment includes an audiotape, other user information, and a child-resistant disposal tray. It comes in 7-milligram, 14-mg, and 21-mg strengths as part of a "step-down" plan to gradually reduce the nicotine level as treatment progresses. Heavy smokers (more than 10 cigarettes a day) start with 21 mg for six weeks, while light smokers (10 or fewer cigarettes a day) start at 14 mg. After six weeks, consumers are to lower their dose for two weeks, with heavy smokers lowering th eir dose a second time. Skin irritation or redness may occur where the patch is placed on the skin. Users should stop using the product if the skin irritation persists or if they have irregular heartbeat, palpitations, or other symptoms of nicotine overdose, such as nausea, vomiting, dizziness, and weakness. People who have significant heart disease or take certain prescription drugs for depression or asthma should seek their doctor's advice before using either patch. The Nicotrol Transdermal System is marketed by McNeil Consumer Products Co. of Fort Washington, Pa., for Pharmacia Upjohn Inc. of Kalamazoo, Mich. The NicoDerm CQ is marketed by SmithKline Beecham Consumer Healthcare of Pittsburgh for ALZA Corporation of Palo Alto, Calif. (For more on nicotine patches, see "Prescriptions to Help Smokers Quit" in the December 1992 FDA Consumer.) AIDS Drug Approved in 119 Days The first in a new class of AIDS drugs--non-nucleoside reverse transcriptase inhibitors--was approved by FDA in only 119 days. Viramune (nevirapine) was approved by the agency June 21 for use--in combination with other AIDS drugs--to treat adult HIV patients whose health has deteriorated. The drug interferes with HIV replication in a way similar to the older AIDS drugs AZT (zidovudine, marketed as Retrovir), ddC (zalcitabine, marketed as Hivid), ddI (didanosine, marketed as Videx), and d4T (stavudine, marketed as Zerit). Viramune must be used in combination with at least one of these other AIDS drugs. Studies showed that AZT and ddI, combined with Viramune, were more effective than AZT and ddI alone in improving health indicators like CD4 cell counts (an indicator of immune system strength) and the amount of HIV detected in the bloodstream. When Viramune was used alone, the virus quickly became resistant to treatment. Viramune's most significant side effect is a rash. According to the drug's labeling, treatment should be discontinued if patients develop a severe rash or a rash with fever, blistering, oral lesions, swelling, muscle or joint aches, general weakness, or conjunctivitis (inflammation in the eyes). To decrease the incidence of rash, patients take a 200-milligram dose of the drug once daily for two weeks, and then start on a 400-mg dose. The drug manufacturer, Boehringer Ingelheim Pharmaceuticals Inc., of Ridgefield, Conn., is conducting studies of Viramune's safety and effectiveness in children with HIV. (See also "Living with Aids: New Treatments Give Hope," in the January-February 1992 FDA Consumer.) First Urine Test for HIV The first HIV test that uses urine samples has been licensed by FDA. Previous HIV tests use either blood or oral fluid samples. The manufacturer, Calypte Biomedical Corporation of Berkeley, Calif., will market the new test as the Calypte HIV-1 Urine EIA. It will also be marketed by Seradyn Inc. of Indianapolis as the Seradyn Sentinel HIV-1 Urine EIA. The new test uses an enzyme-linked immunosorbent assay (ELISA) method to detect the presence of antibodies to HIV-1, the virus that causes the vast majority of U.S. AIDS cases. While it is licensed to screen for HIV-1 infection, it may also be useful for medical purposes when the collection of blood samples is impractical. It is not licensed for blood donor screening, which requires more accurate ELISA blood tests. Only doctors may order the test, and certified medical laboratories will analyze samples. Any initially reactive sample will be retested twice. If even one retest is reactive, the test will be considered positive, although this positive finding does not always indicate HIV infection. For confirmation of a positive urine test, the person must be tested with a more accurate blood test. In clinical studies, 298 patients were diagnosed with AIDS and tested with both the urine test and a licensed ELISA blood test. The urine test was positive in initial screening 99.3 percent of the time. In patients infected with HIV-1 but without symptoms, the urine test would be expected to miss 1 or 2 people in every 100. In other studies in people without HIV-1 antibodies in their blood, the urine test gave a false positive result in 1 or 2 in 100 people, compared to 1 in 1,000 with an ELISA blood test. Before being screened with the new urine test, a person will receive a patient information sheet outlining the test's limitations. This is in addition to the usual information on HIV and AIDS already provided before any HIV testing. After reading the sheet, the person will initial a statement confirming they received the pretest counseling, peel off the sample label, and apply it to the urine collection cup. New Drug for AIDS-Related Eye Infection A new drug is available for treating cytomegalovirus (CMV) retinitis, a potentially severe eye infection that can lead to blindness. While other therapies must be given daily, the new intravenous treatment, Vistide (cidofovir), is administered once a week for the first two weeks and then once every two weeks. FDA based its June 26 approval on two studies in a total of 148 patients. One study showed that the retinitis progressed more slowly in patients treated immediately with Vistide than in patients with delayed treatment. The second study showed the drug was effective in patients with relapsing CMV retinitis who had received other therapy previously. Vistide's most significant side effect is potential kidney damage, which can be reduced with the drug Benemid (probenecid) and by hydrating the body to increase its water content. Other side effects included decreased white blood cells, weakness, nausea, diarrhea, and decreased pressure in the eye. Some studies have shown that the drug may cause cancer in rats, but such cancers have not been seen in human studies. Vistide is manufactured by Gilead Sciences Inc., of Foster City, Calif. (See also "Living with Aids: New Treatments Give Hope," in the January-February 1992 FDA Consumer.) FDA Warns Against Using a Mexican Skin Cream Consumers should not use a Mexican facial skin cream because it can cause mercury poisoning, FDA warned last July. The product was taken off the market in July, but consumers may still have some bought previously. Anyone using the product, Crema de Belleza--Manning, should stop at once, contact their local health authority, and see a doctor for a medical evaluation. The cream, labeled in Spanish for reducing facial oil and removing pimples and blackheads, was sold mainly in Mexico, but also in Arizona, California, New Mexico, and Texas--mainly in Hispanic communities. The manufacturer is Laboratories Vide Natural SA de CV., Tampico, Tamaulipas, Mexico. The label lists the ingredient calomel, which is mercurous chloride, a salt of mercury. Because of the toxicity of mercury compounds and because mercury is readily absorbed through the skin, FDA restricts its use in cosmetics. Mercury may be used only as a preservative in eye-area cosmetics at concentrations not exceeding 65 parts per million when there is no safe and effective nonmercurial preservative available for such use. At the time of the warning, the national Centers for Disease Control and Prevention had identified about 200 users of the cream in the four U.S. border states. CDC testing showed elevated mercury levels in more than 80 people who had used the product. At least three people were diagnosed with mercury poisoning. Product samples were found to contain 6 percent to 10 percent mercury by weight. Chronic exposure to mercury salts can cause nervousness, irritability, tremors, weakness, fatigue, memory loss, changes in hearing or vision or taste, nausea, vomiting, diarrhea, kidney damage, and death. The cream was sold in semi-opaque plastic bottles marked as containing 160 milliliters. The bottles, about 6 inches high, have beige plastic caps and red and blue labels. If undisturbed, the contents separate into an upper layer of clear liquid and a lower layer of white solids. Both U.S. and Mexican authorities removed the product from the two markets. Free Backgrounder on Protease Inhibitors A free new backgrounder on proper use of protease inhibitors, a new class of drugs used to treat HIV, is available from FDA. The new backgrounder provides information about appropriate dosing, the similarities and differences of each approved protease inhibitor, storage, potential drug interactions, and treatment options. A fairly technical document, the backgrounder will be of most use to doctors and other health professionals. A free copy of "The Protease Inhibitors--Backgrounder" may be ordered from FDA's Office of AIDS and Special Health Issues by calling (301) 443-0104, by facsimile transmission at (301) 443-4555, or by E-mailing rklein@bangate.fda.gov. Foods in Menu Claims Must Meet FDA Rule Restaurants that include dishes with claims like "low fat" or "heart healthy" on the menu must be able to demonstrate that there is a reasonable basis for believing that the food is qualified to bear this claim, according to standards recently set by FDA. The July 30 final rule for the standards allows restaurant owners considerable flexibility in establishing this reasonable basis and in presenting the information to consumers. However, owners must be prepared to show officials that their menu claims are consistent with the claim definitions established under the Nutrition Labeling and Education Act of 1990. Unlike processed foods, restaurant menu selections don't have to supply complete nutrition information. Also, menu items bearing a claim can be shown to meet the rule by more economical means than the strict standards of laboratory analyses required for processed foods. For example, a restaurant could show that an item was designed to meet the requirements for the claim because it was prepared using a recipe from a recognized health professional association or dietary group, or that the nutritional values for the dish were calculated using a reliable nutrition database. Furthermore, nutrition information can be provided to the consumer by any reasonable means. It does not have to be presented in the "Nutrition Facts" format seen on packaged food labels, nor does it have to appear on the menu. For example, information on the fat content of all menu items that bear fat claims could be compiled in a notebook available to consumers upon request. FDA estimates that the rule's flexibility, limited scope, and compliance date of May 1997 should minimize its economic impact on the restaurant industry. The new menu rules are identical to the standards that have been in effect since May 1994 for nutrient content claims on placards and signs in large and medium-sized restaurants, and since May 1995 for such claims in smaller restaurants. FDA Eases Way for Limited-Market Devices Medical devices used to treat diseases affecting fewer than 4,000 people annually now will be easier and less costly to bring to market, according to a recent FDA policy change. This change is in addition to FDA's orphan drug program. (See "Orphan Products: New Hope for People with Rare Disorders" in the June 1994 FDA Consumer.) The agency announced in a final rule that it will approve rare-disease devices for marketing as long as manufacturers show: * The device will not expose the patient to any significant or unreasonable risk. * The probable benefits outweigh the probable risks. * No comparable treatment is available. * The company would not be able to bring the product to market otherwise. Makers of new medical devices usually must show that products are effective, a requirement that involves controlled clinical studies. The expense of such studies has been a disincentive to medical device firms--most of which are small--to develop products for rare conditions that have a limited market. Manufacturers of rare-disease devices still may be required to do clinical studies to establish safety but will not have to establish effectiveness. To ensure patient protection, such devices may be used only in medical facilities with local institutional review boards that have approved the device for a specific rare disorder. Also, FDA's approval of such a device is valid for 18 months but can be extended in 18-month increments as long as the criteria for a rare-disease device are met. The new FDA rule--called the Humanitarian Device Exemption--was mandated by the 1990 Safe Medical Devices Act, which requires the agency to exempt manufacturers of products that benefit fewer than 4,000 people from effectiveness requirements of medical device law. FDA published the rule in the June 27, 1996, Federal Register. Data Requested on Safety of Laxative Ingredients After recent animal studies indicated a possible link between cancer and two ingredients in over-the-counter laxatives, FDA asked manufacturers for more data to establish the safety of the two ingredients and three similar ones. In a letter dated May 21, 1996, FDA informed the firms it plans to reclassify the five ingredients--phenolphthalein, bisacodyl, senna, aloe, and cascara sagrada--from category I (safe and effective) to category III (more data needed). Studies by the National Toxicology Program (NTP) provided new evidence that phenolphthalein (chemically related to bisacodyl) may cause cancer in rodents and that senna (chemically related to aloe and cascara sagrada) may cause gene or chromosome irregularities. FDA has no adverse reports or other information linking use of the ingredients with cancer in humans. To determine whether the new evidence may translate into a risk for humans, FDA's Carcinogenicity Assessment Committee met twice with manufacturers and NTP representatives. Finding available safety information to be inadequate for a clear assessment, the agency requested the additional data. Products containing the five ingredients may be marketed until FDA publishes a final regulation. Psyllium, castor oil, docusate sodium, and 20 other ingredients are still considered safe and effective components of laxative products. Reforms to Speed New Animal Drugs to Market Recent FDA reforms promise to shorten the time needed for development of new animal drugs and significantly cut the agency's review time for such products. The reforms, announced May 10, include: * encouraging sponsors to meet with FDA reviewers early in a drug's development to encourage a common understanding of data needed and the most efficient way to get data * reviewing submissions in phases * reviewing technical submissions directly, so sponsors can deal with individual FDA reviewers, instead of dealing through an FDA project manager. In addition, FDA will propose rules providing clear, up-to-date guidance on all crucial phases of animal drug development and production processes. Free New Reprints and Spanish-English Brochure Two new FDA Consumer reprints and a new brochure--Spanish on one side, English on the other--are available free from FDA. The publications and their numbers are: * Taking the Fat Out of Food (FDA) 96-2305 * Fighting Fleas and Ticks (FDA) 96-6051 * Cuide la Seguridad de su Bebé: Coma los Quesos Duros En Vez de los Blandos Durante el Embarazo; Keep Your Baby Safe: Eat Hard Cheeses Instead of Soft Cheeses During Pregnancy (FDA) 96-2304S. To order single copies, write to FDA, HFE-88, Rockville, MD 20857. To order 2 to 100 copies, write to FDA, HFI-40, at the same address, or fax your order to (301) 443-9057. Include the publication number. ------------------------------------------------------------------------ Notebook The Notebook: a potpourri of items of interest gathered from FDA news releases, other news sources, and the Federal Register (designated FR, with date of publication). The Federal Register is available in many public libraries. Cocoa butter substitutes made from safflower or sunflower oil, proposed for use in frostings, candy coatings, and sweet toppings, are generally recognized as safe, according to a final FDA rule. The agency based its ruling in part on a comparison of the new substitutes with an existing cocoa butter substitute made from palm oil. (FR July 10) The effective date for certain portions of the regulation requiring medical device manufacturers to report adverse events has been temporarily delayed. The delay will allow FDA to evaluate new issues on the 1995 rule concerning industry burdens and to determine if requirements should be revised. (FR July 31) The first recognized case of group O HIV infection has been reported in the United States, according to the national Centers for Disease Control and Prevention. CDC described the case as a woman who recently came from West Central Africa, where group O HIV is found almost exclusively, accounting for about 6 percent of AIDS cases there. Despite clinical findings consistent with HIV infection, the patient's blood tested negative or inconclusive for HIV over a two-year period. FDA has asked manufacturers of HIV screening tests to develop modified tests that could reliably detect the new strain. Several tests sensitive to group O are in development. For more information about group O HIV, call CDC's National AIDS Hotline, (1-800) 342-2437. (Morbidity and Mortality Weekly Report, July 5) Reducing pathogenic microorganisms such as Salmonella in poultry and meat products is the subject of new requirements established in a final rule by the Food Safety and Inspection Service of the Agriculture Department. Under the rule, food establishments must use written sanitation standard operating procedures, slaughterhouses must conduct regular microbial testing and establish reduction standards for Salmonella, and all meat and poultry establishments must implement a system of preventive controls to improve product safety. (FR July 25) Child-resistant packaging has saved hundreds of lives since it was mandated for oral prescription drugs in 1974, according to an article in the Journal of the American Medical Association. Researcher Gregory Rodgers, Ph.D., found that an average of 24 fewer children's deaths from accidental overdose occurred annually from 1974 through 1992. (JAMA, June 4) Bed-wetting, or primary nocturnal enuresis, can continue until age 18, and studies have indicated it can cause low self-esteem, attention deficit, or behavioral problems. Parents of bed-wetting children now can call a National Kidney Foundation hot line at (1-800) 622-9010 to receive free information and a referral to a local physician who treats the condition. ------------------------------------------------------------------------ Investigators' Reports Companies, Employees Answer To Corrupt Milk Practices by Paula Kurtzweil A busy grapevine that kept alive a rumor of an illegal dairy practice wound its way into unexpected territory: FDA. The agency investigated and discovered that the rumor was indeed true. As a result, earlier this year, two Arkansas companies and four individuals were sentenced to fines totaling more than $300,000 for allowing milk contaminated with drug residues and a cancer-causing toxin to enter interstate commerce. Two of the convicted people also were sentenced to jail. All four are now on probation or under supervised release. A fifth man pleaded guilty July 16 to a related charge of accessory after the fact, a misdemeanor. At press time in September, his sentencing hearing had not been set. Their scheme came to light after a milk hauler questioned a Tennessee state milk inspector about a milk cooperative's practice of transporting contaminated bulk milk to a cheese curd manufacturer after milk processing plants had rejected the milk. The milk hauler had learned about the practice from fellow milk haulers, according to former FDA compliance officer Ray McCullough. The milk hauler wanted to know why this particular milk cooperative was allowed to ship contaminated milk when he had to dump his. The milk that went to the cheese curd manufacturer contained residues of the antibiotics penicillin and tetracycline and of sulfa compounds, all of which can be used to treat diseases in cows. However, it is illegal to allow milk contaminated with these drugs into the food supply because the drugs can cause allergic and other adverse reactions in some people. The drugs also may interfere with the effectiveness of human medications and may contribute to the development of drug-resistant bacteria. In addition, one sulfa drug, sulfamethazine, is a potential carcinogen. The milk also contained aflatoxin, which is produced by certain species of mold and may cause liver cancer. The mold can grow on grains used in animal feed, causing the toxin to form. The toxin can then pass into the milk of animals eating the feed. Those sentenced last March for participating in the scheme were: * Associated Milk Producers Inc. (AMPI) Mid-South Division, of Little Rock, Ark. This company, a milk cooperative, is a division of one of the largest milk-producing associations in the United States, according to McCullough. Each division is made up of dairy farmers who sell their raw milk to milk processing plants. AMPI collects the milk and transports it to processing plants for the farmers. * Hills Valley Foods Inc., of Batesville, Ark. This company made cheese curd, an intermediary substance in cheese production, and sold it to a Missouri cheese company. * Jerry Moore, manager of AMPI's Mid-South Division * John Wilbanks, president of Hills Valley Foods * Darrell Williams, laboratory supervisor for AMPI's Mid-South Division * Larry Miller, dispatcher and administrative assistant for AMPI's Mid-South Division. In addition, Jerry Griggs, milk movement coordinator for AMPI's Southern Region office, in Arlington, Texas, pleaded guilty in the U.S. District Court for the Eastern District of Arkansas. FDA got involved in the case when the Tennessee Department of Agriculture reported the milk hauler's allegations to the agency in fall 1990. Typically, milk haulers collect raw milk from farms and take it to processing plants via bulk tanker trucks. Each tanker holds about 20 metric tons (45,000 pounds) of milk, worth about $8,000, and milk from one to as many as nine farms can be put into one tanker, depending on the amount of milk from each farmer, McCullough said. Before haulers unload the milk, the processing plant screens each truckload for chemical contaminants, bacteria, and other quality factors. If the milk tests positive for drug residues or aflatoxin, it must be dumped. According to the milk hauler's allegations, this was the point at which AMPI truck drivers shipped milk that tested positive for illegal drug residues or aflatoxin to Hills Valley Foods rather than dump it. FDA began to investigate the allegations in October 1990. McCullough, along with other FDA investigators, interviewed a number of employees with Hills Valley Foods and AMPI, including laboratory personnel, dispatchers, and milk truck drivers. The investigators reviewed recorded test results of milk samples, milk deliveries, and routing information. With this information, they compiled a computerized database. They then used the database to cross-reference positive drug residue and aflatoxin test results with delivery dates and other pertinent information. The cross-references enabled them to show that contaminated milk was shipped to Hills Valley Foods, where it was made into cheese curds and then shipped to the Missouri cheese maker. As a result of these findings, the U.S. Attorney's Office undertook a grand jury investigation in June 1993, subpoenaing about 50 witnesses, including AMPI and Hills Valley employees who had refused earlier to cooperate with FDA investigators. The grand jury charged that: * AMPI Mid-South Division had an agreement with Hills Valley Foods in which AMPI sold rejected contaminated milk to Hills Valley. According to FDA investigators, Hills Valley bought the contaminated milk at a favorable price. * The scheme involved hundreds of thousands of pounds of contaminated milk sold on about 30 occasions between about December 1987 and about April 1993. * Employees often changed positive test results for antibiotics and aflatoxins to negative results. This finding, according to FDA's McCullough, was borne out by U.S. Postal Service forensics laboratory testing that enabled investigators to decipher erased original entries. * Employees Moore and Williams instructed truck drivers to call ahead to Hills Valley to inform personnel that a "hot," or contaminated, load of milk was on its way. This preannouncement signaled Hills Valley personnel that they would have to add an extra dose of starter culture (called "hot shot" by both parties) to prevent the drugs in the milk from inhibiting the bacterial culture needed to make cheese. * AMPI identified farmers whose milk had contaminated each truckload, and Moore and Williams would arrange for direct pickup of that farmer's milk for delivery to Hills Valley. In June 1995, a grand jury for the U.S. District Court for the Eastern District of Arkansas indicted the two companies and four individuals on charges related to the distribution of contaminated milk. In November 1995, Moore, AMPI's division manager, signed a plea agreement, acknowledging guilt to a one-count felony conspiracy charge and agreeing to cooperate in the grand jury's investigation. He was sentenced Feb. 29, 1996, to five months in prison, five-months' home detention, and three years of supervised release and was fined $20,000. Five other parties pleaded guilty to misdemeanor offenses throughout 1995 and 1996 and were sentenced in March 1996 as follows: * AMPI Mid-South Division--fined $200,000. * Hills Valley Foods--fined $88,000 and placed on two years' probation. * John Wilbanks of Hills Valley Foods--sentenced to 30 days in the county jail, five-months' home detention, and seven months of other supervised release; fined $20,000. * Darrell Williams of AMPI--one year of probation; fined $2,500. * Larry Miller of AMPI--one year of probation; fined $5,000. Paula Kurtzweil is a member of FDA's public affairs staff. ------------------------------------------------------------------------ Cream Doesn't Pay A Wyndmere, N.D., husband and wife learned that "cream doesn't pay"--at least not if a cheaper fat is used in place of the real thing. The couple were sentenced to probation, fines and community service for selling soybean oil labeled as "farm cream." Clayton Rawhouser, 46, was sentenced Feb. 6, 1996, to two years' supervised probation, plus two and a half months in jail (which he served while awaiting sentencing), and 50 hours of community service. He also was ordered to pay a $75 special assessment. Janice Rawhouser, 45, was sentenced Nov. 28, 1995, to six months' unsupervised probation, fined $250, and ordered to pay a $50 assessment. A grand jury in the U.S. District Court for the District of North Dakota had indicted the couple on 48 counts of mail fraud, obstruction of justice, and shipping adulterated and misbranded farm cream across state lines. Both Rawhousers pleaded guilty to lying to a U.S. Customs agent and introducing misbranded or adulterated food into interstate commerce. The North Dakota Department of Agriculture notified FDA's resident post in Fargo about a problem the state's assistant dairy commissioner, Tom Haak, discovered during a routine inspection of Wyndmere Creamery on Jan. 26, 1994. Haak had found bills of lading showing that since Jan. 1, the creamery had imported more than 563 metric tons (1.25 million pounds) of raw cream from Mexico. This violates the federal Milk Importation Act, which prohibits importing milk and cream from Mexico because these products do not meet American health standards. The inspector returned two days later with a state-issued embargo for all cream and butter products at the dairy. On Feb. 1, Haak returned to Wyndmere Creamery with Howard Burmeister, an investigator with FDA's Fargo resident post, to obtain product samples and copies of records. Clayton allowed them to take samples, but would not give them access to any records and ordered them off the premises. The next day, Burmeister and a county deputy sheriff arrived at the dairy with a subpoena from the state of North Dakota ordering the surrender of all pertinent records. "No records were found in the search," said Jess Talty, special agent with FDA's Office of Criminal Investigations in Chicago, "and neither was Clayton. He had taken off, and Janice said she burned the records Jan. 31." In response to a request from the Rawhousers' attorney, the North Dakota Department of Agriculture offered to settle with Wyndmere Creamery if the creamery gave the department information about the illegal importation of Mexican cream and paid for disposing of the finished product in North Dakota and in Chicago, where it had been sold to Danish Maid Butter Co. between Oct. 27, 1993, and Jan. 31, 1994. The dairy rejected the offer. "The burning question was how FDA and U.S. Customs could have allowed 26 semi-truckloads of Mexican cream to be smuggled across the border," Talty said. "The answer was 'we didn't, and it wasn't': There never was any imported Mexican cream." FDA Special Agents Daniel Piovosi and Greg Aspinwall learned this when they went back to the creamery on Feb. 23 to interview Janice Rawhouser and dairy employees. According to Talty, Rawhouser said the creamery had never used Mexican cream. Instead, she said, they used cream from smaller nearby farms. "She said she wouldn't tell anyone where they got the cream because they didn't want their employees to find out and start their own business," Talty said. "As we talked to the employees, though, we got the impression that it was almost impossible for the dairy to process the amount of cream the Rawhousers were bringing in and shipping out in such a short period of time." In reviewing phone and trucking records and talking to employees, the investigators found the creamery had had many transactions with Honeymead Soybean Oil Co., in Mankato, Minn. Talty and U.S. Customs Special Agent Anthony Onstad interviewed officials at Honeymead on March 9 and learned that Clayton Rawhouser had set up contracts to buy 116 metric tons (257,460 pounds) of soybeans in November 1993, 261 metric tons (579,360 pounds) in December 1993, 315 metric tons (700,280 pounds) in January 1994, and 394 metric tons (875,000 pounds) each in February, March and April 1994. Meanwhile, laboratory results of samples taken during the Feb. 1 inspection at Wyndmere and from Danish Maid on Feb. 3 showed the "farm cream" in fact was mostly soybean oil with some food coloring added to make the product look like cream. On Feb. 22, 1995, FDA's Office of Criminal Investigations (OCI) turned the information over to the Department of Justice, which presented the case to the grand jury Sept. 8, 1995. OCI special agents arrested Janice Rawhouser Sept. 9 but continued to look for Clayton Rawhouser, who officials believe fled the state around March 1994. Talty located an address for Rawhouser in Pharr, Texas, and notified OCI's Austin, Texas, office. On Sept. 12, 1995, Special Agent Ray Strucker, along with an agent from U.S. Customs and a U.S. marshal, went to the address, which turned out to be a storage facility. "The owner wouldn't give them any information, so they went back to the Customs Office to get a summons to serve him with," Talty said. "Then they went back to the warehouse and, lo and behold, who should come driving up right in front of the place but Clayton." Clayton Rawhouser was arrested in Pharr on Sept. 12 and held in jail until his sentencing. --Marian Segal ------------------------------------------------------------------------ Food Analyst in Prison for Falsifying Data For falsifying data from tests on food samples salvaged from a warehouse fire, a Massachusetts consultant received a two-year prison sentence, a $10,000 fine, and three years of supervised release. George T. Michael, 51, of Dedham, Mass., pleaded guilty to one count of wire fraud related to the scheme and one count of making false statements to secure a bank loan at his March 12 sentencing. Michael's scheme began following a December 1991 fire in the Americold facility, a 100-acre underground storage cave in Kansas City, Kan. The facility housed millions of pounds of food products owned by various clients. Damage estimates from the fire ranged as high as $1 billion. Insurers paid off food owners' claims; then, to recoup some of the losses, they hired salvagers to determine what food could be resold. In early 1992, a salvage company, M.F. Bank and Co. Inc., hired Michael to oversee chemical analyses of more than $2 million worth of food. The company wanted Michael to verify if the products had been contaminated with toxic substances from the fire. The tests would determine whether the food had to be destroyed or could be released to the public. Michael subcontracted with Minnesota Valley Testing Laboratories (MVTL) in New Ulm, Minn., to perform the analyses. The food was supposed to be tested for benzene, toluene, styrene, xylene, and polychlorinated biphenyls (PCBs). Contamination from any of these chemicals would render the food unsuitable for human consumption. The Kansas Department of Health and Environment (KDHE) oversaw the fate of the warehouse food, basing its decisions on submitted test results. On Oct. 6, 1992, the department called Greg Dixon, an investigator in FDA's Kansas City district office to discuss sample data. KDHE officials reported that Michael had submitted a laboratory report on MVTL letterhead that read "none detected" for various contaminants, yet no levels of sensitivity for the tests were listed, as is common practice. "This made us and KDHE suspicious of the accuracy of Michael's data," Dixon says. FDA's Kansas City district then asked the agency's Minnesota district office to investigate the Minnesota laboratory. After interviewing the analyzing chemist at MVTL, Minnesota district investigators concluded that because not all the tests indicated on Michael's lab report had been done, Michael must have falsified results. On Nov. 23, 1992, FDA's Minnesota district office completed its investigation of the testing laboratory, which included interviews and reviews of records. The investigation confirmed that Michael had submitted false test results to KDHE. Officials determined neither the laboratory nor the salvage company that hired Michael was involved in Michael's scheme. In September 1995, the U.S. District Court for the District of Massachusetts charged Michael with the two criminal counts. The court charged a wire fraud violation because Michael transmitted the false results over a facsimile machine. The other count was for obtaining a loan in 1988 from a Massachusetts savings and loan by providing false statements. --John Henkel ------------------------------------------------------------------------ Alcohol-Free Mouthwash with Twist of Bacteria A chemical company recalling contaminated mouthwash called on the specialized services of a water company to help get the mouthwash maker out of hot water. Hydrox Chemical Co., of Elgin, Ill., hired Culligan Water Co. following an FDA investigation that faulted Hydrox for failing to maintain its purified water system. Unmaintained for almost a year, the system apparently introduced the bacterium Pseudomonas cepacia into hundreds of thousands of gallons of Fresh Moment Alcohol Free Mouthwash produced by Hydrox between August 1995 and February 1996. The mouthwash was distributed to hospitals across the country and caused infection in 12 hospitalized patients on ventilators. While rarely harmful to healthy people, Pseudomonas cepacia can be dangerous to people with depressed immune systems. Laboratory analyses identified the bacteria in samples of the mouthwash. The company voluntarily began recalling the mouthwash in February, and by August, all of it had been recalled. FDA became aware of the contamination last Feb. 2, when a epidemiologist with Froedtert Lutheran Memorial Hospital in Milwaukee contacted the agency. He reported that since Dec. 20, 1995, 12 hospital patients--all on ventilators--developed Pseudomonas cepacia infections. The hospital laboratory identified the bacterium in patients' sputum and in bottles of Hydrox's Fresh Moment mouthwash, which was distributed to patients. A doctor caring for the ventilator patients became suspicious after noticing that a number of patients developed rashes around their mouths, where their face masks rested. Health-care workers had used the mouthwash to swab patients' throats. All the patients recovered from the infection following antibiotic treatment. FDA traced the manufacture of the mouthwash to Hydrox, which also makes other cosmetics, over-the-counter drugs, and veterinary products. Theodore Thorsen, an investigator with FDA's Chicago district office, inspected the company's facility Feb. 2. He collected samples of the company's mouthwash, as well as other company products, such as body lotions, baby shampoo, and milk of magnesia antacid and laxative. FDA's Midwest Laboratory for Microbiological Investigations analyzed the samples and identified Pseudomonas cepacia in the mouthwash. The other products tested negative for bacterial contamination. Thorsen continued to inspect and monitor the company's activities through February and March. His inspections identified six problems: * The purified water system had not been properly cleaned and tested since May 1995. Hydrox's president, Kapana Ramanandan, told FDA officials the company skipped the scheduled maintenance because it couldn't afford it. The company filed for bankruptcy in March 1995, under Chapter 11 of the Federal Bankruptcy Act. * The reverse osmosis membranes of the water system had not been changed for more than a year, although this should be done every four months, according to the company's written procedure, to prevent microbial buildup. The company again cited financial difficulties as the reason. * Employees failed to perform adequate microbial challenge tests--specifically of Pseudomonas cepacia, which can flourish in the presence of the antibacterial agent the company added to its Fresh Moment mouthwash. * Employees did not use the appropriate hose clamps on equipment. Thorsen noted that the clamps used "appeared to be basic hose clamps that are used in the automotive trade" and were rusty, dirty and discolored. * Employees left doors open during production, allowing airborne dust from outside to enter the manufacturing area. By Feb. 23, Hydrox had taken steps to correct problems, according to a Feb. 13 letter Hydrox president Ramanandan sent to FDA's Chicago district office and a conference he had with FDA officials on Feb. 23. Chief among his actions was to contact Hydrox's mouthwash customers--hospitals, medical device repackers, and clinics--and request that they return mouthwash made between July 1, 1995, and Feb. 2, 1996. The company relied on product coding and invoices to identify customers that had received contaminated lots. By testing mouthwash in reserve, the company traced the point at which contamination began to the end of August. The company decided to extend the cutoff point to July 1 as a precaution. Ramanandan also said the company had: * contracted with the Culligan Water Co. for $30,000 to reengineer, validate and maintain Hydrox's water purification system * sanitized the entire water system with hydrogen peroxide * changed the reverse osmosis membranes * rewrote the standard of operation for the purified deionized water system * replaced hoses and clamps with new sanitary connectors. Ramanandan also said the company would train employees on the need to keep doors closed during production. On April 4, 1996, FDA issued company president Ramanandan a warning letter because of "concern over this matter," wrote Raymond Mlecko, FDA's Chicago district director. He cited the company's manufacture of other products with water from the same system used to make mouthwash and the company's refusal to perform routine equipment maintenance when scheduled. Mlecko warned the company that failure to correct problems could result in enforcement action, such as a seizure or injunction. The company responded in a May 9 letter reiterating the corrective measures it had taken. FDA's Thorsen continues to monitor the company. According to Kathy Haas, recall coordinator for FDA's Chicago district office, the company had recalled all of the affected products by Aug. 1. The company destroyed the mouthwash at a landfill, she said. --Paula Kurtzweil ------------------------------------------------------------------------ Summaries of Court Actions Summaries of Court Actions are given pursuant to Section 705 of the Federal Food, Drug, and Cosmetic Act. Summaries of Court Actions report cases involving seizure proceedings, criminal proceedings, and injunction proceedings. Seizure proceedings are civil actions taken against goods alleged to be in violation, and criminal and injunction proceedings are against firms or individuals charged to be responsible for violations. The cases generally involve foods, drugs, devices, or cosmetics alleged to be adulterated or misbranded or otherwise violative of the law when introduced into and while in interstate commerce. Summaries of Court Actions are prepared by Food and Drug Division, Office of the General Counsel, HHS, and are published by direction of the Secretary of Health and Human Services. ------------------------------------------------------------------------ SEIZURE ACTIONS Food/Contamination, Spoilage, Insanitary Handling PRODUCT: Alcobaca Portugal broad beans and fava beans, canned, at Milford, Ill. (C.D. Ill.); Civil No. 92-2195. CHARGED 6-30-92: While held for sale after shipment in interstate commerce at the Fremont Company, in Milford, Ill., the articles were adulterated in that they consisted of insects and insect-damaged beans--402(a)(3). The articles were also adulterated in that they were prepared and packed under insanitary conditions whereby they might have become contaminated with filth--402(a)(4). DISPOSITION: A default decree of condemnation and destruction ordered the articles destroyed. (F.D.C. No. 66443; S. No. 92-610-596; S.J. No. 1) PRODUCT: Flounder fillets, frozen, at Newport News, Va. (E.D. Va.); Civil No. 4:95CV00125. CHARGED 9-6-95: While held for sale after shipment in interstate commerce at Top Quality Seafood, Inc., in Newport News, Va., the articles were adulterated in that they consisted of decomposed fish--402(a)(3). DISPOSITION: A consent decree of condemnation and destruction ordered the articles destroyed. (F.D.C. No. 67104; S. No. 95-733-868; S.J. No. 2) PRODUCT: Fresh plate fish, frozen, at Columbus, Ohio (S.D. Ohio); Civil No. C2-89-125. CHARGED 2-13-89: While held for sale after shipment in interstate commerce at Interstate Cold Storage, Inc., in Columbus, Ohio, the articles were adulterated in that Smooth Oreo Dory was substituted for Orange Roughy--402(b)(2). The articles were misbranded in that they were offered for sale under the name of another food, and labeling failed to bear the common name of the food--403(b) and 403(i). The articles were also misbranded in that their labeling was false because the food was labeled as Orange Roughy when it was Smooth Oreo Dory--403(a)(1). DISPOSITION: The articles were donated to a charitable organization. (F.D.C. No. 65619; S. No. 89-547-961; S.J. No. 3) PRODUCT: Raisins, at Selma, Calif. (E.D. Calif.); Civil No. CV-F-94-5689-GEB-SSH. CHARGED 7-5-94: While held for sale after shipment in interstate commerce at American Raisin Packers, Inc., in Selma, Calif., the articles were adulterated in that they consisted of insects, insect fragments, insect cast skins, and feather barbules--402(a)(3). The articles were misbranded in that they were manufactured from two or more ingredients, and their label failed to bear the common name of each ingredient--402(i)(2). DISPOSITION: A consent decree ordered the articles destroyed. (F.D.C. No. 66984; S. No. 94-705-349; S.J. No. 4) PRODUCT: Shrimp, frozen, at Tampa, Fla. (M.D. Fla.); Civil No. 95-1877-Civ-T-23(A). CHARGED 11-14-94: While held for sale after shipment in interstate commerce at Seaboard Cold Storage, in Tampa, Fla., the articles were adulterated in that they consisted of decomposed shrimp--402(a)(3). DISPOSITION: A consent decree of condemnation and destruction ordered the articles destroyed. (F.D.C. No. 67111; S. No. 95-713-265; S.J. No. 5) Drugs/Human Use PRODUCT: Broncho saline, sterile, at Evansville, Ind. (S.D. Ind.); Civil No. EV-91-83. CHARGED 6-18-91: While held for sale after shipment in interstate commerce at Blairex Laboratories, Inc., in Evansville, Ind., the articles were adulterated in that they were unapproved new drugs--505(a). The articles were misbranded in that they were represented to be a drug, sodium chloride inhalation solution, which is recognized by the U.S. Pharmacopeia, but they were not packaged and labeled in single-dose containers as required by the U.S. Pharmacopeia--502(g). DISPOSITION: A consent decree of condemnation ordered the articles destroyed. (F.D.C. No. 66083; S. No. 91-555-243/244; S.J. No. 6) Medical Devices PRODUCT: Thor of Genesis I, vibrational sound instrument, at South Euclid, Ohio (N.D. Ohio); Civil No. 1:93CV1724. CHARGED 8-17-93: While held for sale after shipment in interstate commerce at the Window of Mind Bookstore in South Euclid, Ohio, the article was adulterated in that it was a class III device without an application for premarket approval--501(f)(1)(B). The article was misbranded in that its labeling was false and other information regarding the article was not provided as required--502(a) and (o). DISPOSITION: The article was destroyed. (F.D.C. No. 66704; S. No. 93-670-674; S.J. No. 7) INJUNCTION ACTIONS DEFENDANTS: Big E Industries, Rio Arriba Minerals, Inc., Action Trading Company, Inc., and Harvey L. Earles, at Oklahoma City, Okla. (W.D. Okla.); Civil No. Civ-89-957-W. CHARGED 5-31-89: The defendants introduced and delivered into interstate commerce adulterated industrial grade/inedible oils and blended feeding fat--301(a). The industrial grade/inedible oils were adulterated in that statements warning of their inferior quality were removed--301(k). The defendants also adulterated blended feeding fat, which is used as an ingredient in animal feeds, in that it was unfit for food and its inferior quality was concealed--402(a)(3) and 402(b)(3). DISPOSITION: The parties were ordered by the court to enter into an agreement calling for written standard operating procedures. The company subsequently was found to be in compliance with the court's order. (Inj. No. 1207; S. No. 89-527-364/367; S.J. No. 8) DEFENDANT: Frank Gasper, at Tulare, Calif. (E.D. Calif.); Civil No. 96-5443-REC DLB. CHARGED 4-29-96: The defendant introduced or caused to be introduced into interstate commerce adulterated calves for slaughter for use as food--301(a). The calves were adulterated in that they contained unsafe new animal drugs--402(a)(2)(D). The calves were also adulterated in that they were held under insanitary conditions whereby they might have been rendered injurious to health--402(a)(4). DISPOSITION: A consent decree of permanent injunction was filed. The defendant later was found to be in compliance with the decree. (Inj. No. 1392; S. No. 95-753-841; S.J. No. 9) MISCELLANEOUS ACTIONS ACTION: Henley v. FDA, at Mineola, N.Y. (2d Cir.); Civil No. CV 93-5389. CHARGED 11-26-93: Plaintiff-appellant requested that FDA require oral contraceptive manufacturers to include in the labeling of their product the following warning statement: "Estrogen has been shown to cause cancer in animals." FDA denied the petition and a subsequent petition for reconsideration. The district court granted a summary judgment in favor of the defendant and denied the plaintiff's cross-motion for summary judgment. DISPOSITION: Plaintiff appealed. The appellate court affirmed the district court's ruling. Plaintiff did not file a petition for certiorari. (Misc. No. 1016; S.J. No. 10) ACTION: Public Citizen, Inc. v. DHHS, et al., at Washington, D.C. (D.D.C.); Civil No. 1:94CV02338. CHARGED 10-28-94: Plaintiff charged that FDA had unreasonably delayed publishing regulations under the Safe Medical Devices Act of 1990. DISPOSITION: While in litigation, three of the four regulations the plaintiff was suing over were published--510(k) summary/statement, civil money penalties, and medical device reporting. Plaintiff lost on the remaining claim relating to postmarket surveillance. Plaintiff was awarded a settlement under the Equal Access to Justice Act. (Misc. No. 1075; S.J. No. 11) ------------------------------------------------------------------------ Correction: S.J. No. 5 in the April 1996 FDA Consumer Summaries of Court Actions stated (in the Disposition) that Duramed Pharmaceutical entered into a consent decree of permanent injunction. The consent decree was subsequently dissolved by the U.S. District Court for the District of Maryland on Jan. 2, 1996. ------------------------------------------------------------------------ ------------------------------------------------------------------------ FDA Consumer is the official magazine of the U.S. Food and Drug Administration. Each issue contains in-depth feature articles written for the general public on FDA-related health issues. The magazine also includes reports from FDA's own investigators that go behind the scenes to show how the agency protects the public from unsafe or worthless products. FDA Consumer is published monthly, except for combined issues for July-August and January-February. Subscriptions are available for $15 per year by writing: Superintendent of Documents Government Printing Office Washington, DC 20402-9371. ------------------------------------------------------------------------