FDA approved Monsanto Company's recombinant bovine growth hormone (bovine somatotropin or rbST product in November 1993 after a comprehensive review of the product's safety and efficacy, including human food safety. The safety of milk from rbST treated cows was clearly demonstrated. Since marketing of Monsanto's product began in February, CVM has received numerous inquiries from consumers concerned about this product. The following are answers to some of the questions we have received on the product which is being marketed under the name of POSILAC ®.

How does FDA determine the safety and efficacy of new animal drugs such as POSILAC?

In order for a new animal drug to be approved for marketing the U.S., the sponsor must establish that it is effective and safe. Effectiveness means that the drug does what the company claims (for example, increases milk production). Safety covers three main areas: safety of the food products to humans, safety to the target animal (the cow), and safety to the environment. In addition, companies must prove to FDA that they can consistently manufacture the drug to a specific potency and purity.

Drug sponsors must submit to their New Animal Drug Application (NADA) data to determine the safety and effectiveness of the drug product. In cases where data required by FDA to make decisions are not otherwise available, the drug sponsor is responsible for providing the data. The drug sponsor may conduct the study or may have the research performed by a contract laboratory. FDA has neither the legal authority nor the resources to do the drug testing on its own.

FDA takes a number of steps to monitor the reliability of data submitted to an NADA. Before sponsors conduct their studies, they usually submit study protocols to FDA. In this way, the FDA can comment on the adequacy of the studies and recommend any changes or additions that are necessary. Although the sponsors fund and monitor safety and effectiveness studies, the majority of the trials are conducted by independent scientists at universities, research laboratories, or commercial farms. FDA also has a Bioresearch Monitoring Program which allows FDA inspection of safety and effectiveness studies while they are ongoing. Finally, sponsors must submit their raw data to the NADA so that FDA can check the accuracy and completeness of the summary results that were derived and the statistical methods used.

Is the milk from cows treated with rbST any different from milk from untreated cows?

No. Milk from cows treated with POSILAC is not different from milk of non-treated cows. It has the same nutritional benefits as any other milk. It is safe for the consumer.

How do you know that rbST is safe for humans who consume meat and milk from treated cows?

FDA only approved POSILAC after concluding that its use poses no risk to human health. Cows produce bovine somatotropin in their pituitary glands. Thus, we have been naturally exposed to trace levels of bST in beef, milk, and other dairy products. Because it is a protein hormone, bovine somatotropin is broken down during digestion, which renders it biologically inactive and incapable of having an effect in humans. Intact proteins are not absorbed into the body. Even if injected into humans, bST has no effect. In the 1950s, studies were done to look at natural bST as a possible treatment for human dwarfism. The hormone had no effect on those treated. An additional assurance of safety is that heating, such as with cooking and pasteurization, inactivates bST that may be present in milk or meat. In addition to FDA, a panel of independent medical and veterinary experts at a National Institutes of Health (NIH) Technology Assessment Conference in December 1990, concluded that milk derived from cows treated with rbST is safe for human consumption. Also, the Office of Technology Assessment (OTA) released a report in May 1991 entitled U.S. Dairy Industry at a Crossroad: Biotechnology and Policy Choices. The report analyzes technologies, particularly bovine somatotropin, that would likely be available to the dairy industry in the 1990s. In the report, which was prepared at the request of Congress, OTA agreed with FDA's decision that food from cows treated with bovine somatotropin poses no additional risk to consumers. The World Health Organization (WHO) Joint Expert Committee on Food Additives in 1992 also confirmed FDA' s conclusion that the food products from rbST-treated cows are safe for humans, as have the American Medical Association and the drug regulatory bodies of the European Union and other countries including Canada, Mexico, and the U.K .

What about the possibility that insulin-like growth factor 1 in milk from treated cows will lead to increased rates of breast cancer and other human health problems?

FDA and other scientific and regulatory bodies have thoroughly examined the safety of milk produced by rbST-treated cows and have concluded that it is safe. There is absolutely no possibility that the consumption of milk from rbST-treated cows could increase the risk of breast cancer. Insulin-like growth factor 1 (lGF-1) is a natural protein which mediates many of somatotropin's actions. It is required for normal growth and possibly health maintenance. IGF-1 is structurally and chemically similar to insulin and is normally present in most body tissues and fluids including human breast milk and saliva.

The consumption of dietary IGF-1 plays no role in either inducing or promoting any human disease, nor does it cause malignant transformations of normal human breast cells. Abnormally low levels of IGF-1 are associated with several disease conditions including dwarfism, malnutrition, osteoporosis and infertility. It has also been suggested that a decline in IGF-1 levels in human tissue causes many of the degenerative changes associated with aging.

Levels of IGF-1 in cow's milk and meat are very much lower than the levels found naturally in human blood and other body tissues. The IGF-1 occurs naturally in human breast milk at about the same concentration as that found in cow's milk. FDA has reviewed several comprehensive studies to determine if administering rbST in cows affects the IGF-1 content of their milk. These studies have demonstrated that rbST does not increase the IGF-1 content above levels normally found in milk of non-treated animals.

IGF-1 in milk and meat is not absorbed intact. Dietary IGF-1 in milk and meat is broken down in the gastrointestinal tract by digestion. Undigested IGF-1 is excreted in the feces.

The suggestion that IGF-1 in milk can induce or promote breast cancer in humans or premature growth stimulation in infants is scientifically unfounded. Milk from rbST-treated cows is safe for human consumption.

How can FDA be sure that mastitis caused by using rbST in cows will not lead to increased antibiotic use and antibiotic residues in milk?

Cows treated with POSILAC have a slightly increased risk of mastitis, a common infection of the udder, and antibiotics are often used to treat mastitis. However, FDA has concluded that the increased risk to human health posed by mastitis and the resulting use of antibiotics is insignificant. The effect of POSILAC treatment on the incidence of mastitis is much less than other factors, such as the season, age of the cows, and herd-to-herd variation. For example, the increase in mastitis incidence from winter to summer is at least nine times greater than the increase due to POSILAC treatment.

Another important factor is that therapeutic drugs, such as antibiotics for the treatment of mastitis, are to be used in food-producing animals only under approved conditions and with appropriate milk and meat withdrawal periods (as established by FDA) to ensure that food products are safe for human consumption.

Federal and State programs require milk to be tested for drug residues, and milk found to have unsafe levels of residues must be discarded. Further, producers responsible for violative residues are subject to severe regulatory sanctions.

FDA's Veterinary Medicine Advisory Committee and expert consultants met in an open public hearing in March 1993 to discuss the issue of increased mastitis in POSILAC-treated cows and a potential increase in the risk of antibiotic residues in milk. They concluded that the risk to human health was insignificant. Finally, Monsanto has agreed to an extensive post-approval monitoring program to ensure that the use of POSILAC in cows does not lead to an increase in the incidence of violative antibiotic residues in milk.

Why do you think the product is safe when it causes cow health problems?

FDA would not have approved the drug if there were serious risks to the health of the cows. The labeling for POSILAC, which includes precautions and side effects, provides direction to the farmers who use the drug. Such cautions are included on all drugs, and are based on data from pivotal studies submitted by the drug sponsors. These cautions alert farmers to potential problems that might occur with use of the drug. With this information, farmers can decide whether they will try the drug on their farm. If they decide to use the drug, they may use the labeling information to change their management practices, if possible, to help minimize problems associated with the use of the drug.

Cows using POSILAC may have small decreases in gestation length and birth weight of calves. However, this is not considered to be a serious problem, and actually may help make it easier for the cow to give birth. Health and growth of the calves from POSILAC and control cows was similar. In addition, other cow health problems that might be associated with the use of the drug are not considered by FDA to be serious health problems. Also, these problems did not occur at rates that would prohibit the use of POSILAC.

What about the increased "pus" in the milk from cows treated with rbST?

Some individuals are incorrectly using the word "pus" to refer to somatic cells in milk. FDA concluded that the milk somatic cell count (SCC) may increase in some herds when POSILAC is used. Somatic cells are always present in milk and consist of cells (such as epithelial cells, leukocytes, neutrophils, and macrophages) that are already present in the human body and blood. These cells are necessary to fight infection, and the increase noted in some POSILAC-treated cows likely reflects the slight increase in mastitis incidence and mammary cells which slough off during infection. There are no health consequences associated with the consumption of SCC. Also, somatic cells themselves do not change the appearance of milk. The U.S. government imposes a limit on the maximum level of SCC permitted per dairy farm. However, this is not based on a human safety concern, but rather an economic concern. Increased levels of SCC in milk are associated with reduced cheese yields because enzymes released by somatic cells degrade casein in milk. Some Ssates and dairy processors offer financial bonuses to farmers who produce milk with low SCC. Thus, there are substantial financial incentives for dairy farmers to maintain low SCC levels in their milk.

Why didn't FDA require Monsanto to develop a test to determine whether milk comes from treated cows?

FDA did not require Monsamo to develop such a test because the milk from cows treated with POSILAC has been determined to be safe for human consumption. Since there is no human food safety concem, FDA has no grounds on which to demand such a special identification test. While developing such a test is theoretically possible, it would also be useless for regulatory purposes.

Why aren't you requiring that milk and meat from treated cows be labeled as such?

FDA cannot require special labeling of products from cows treated with POSILAC because the Agency has concluded that it lacks a basis under the law to require special labeling of such foods. Milk from treated cows is the same as milk of untreated cows. However, voluntary labeling is permitted if it is truthful and not misleading. In response to requests from several State, industry, and consumer represematives, FDA has published interim Guidance on voluntary labeling of products from cows that have not been treated with rbST. This interim guidance was published in the Federal Register on February 10, 1994.

Why did the FDA approve this drug to increase milk production when we already have too much milk?

By Federal law, social and economic needs for a drug cannot enter into FDA's approval decision. However, in its budget reconciliation bill, Congress included a 9O-day moratorium on the sale of rbST following FDA approval. During the 90-day period, the Office of Management and Budget (OMB) conducted a study to address these economic concerns.

In their report, "Use of Bovine somatotropin (rbST) in the United States: Its Potemial Effects," OMB stated that income for individual farmers who use bST is likely to increase for both small and large farms. They also believed bST use would increase U.S. milk production by about one percent through Fiscal Year 1999. This would likely lead to slightly lower prices for milk, leading to declines in aggregate dairy farm income by about one percent over the same period. OMB stated that the lower milk prices from bST use are expected to contribute to higher Federal Government dairy price-support costs. Federal dairy price-support program costs are expected to increase by approximately $150 million in the peak year, Fiscal Year 1996, and decline in later years. However, lower milk prices are expected to decrease costs for nutrition programs like Food Stamps and the Special Supplemental Food Program for Women, Infants, and Children (WIC). According to OMS, savings in the costs of Federal feeding programs could begin in Fiscal Year 1997, and could completely offset the increased cumulative costs of the Federal dairy price-support program over 10 years. Therefore, approval of animal drugs to improve production helps ensure a bountiful food supply for our children and grandchildren.

Why did FDA approve this drug for use in the U.S. when it is banned in Europe?

The European Community imposed a one-year moratorium on the use of rbST on economic and political grounds. This had nothing to do with rbST safety. In January 1993, the Committee for Veterinary Medicinal Products of the European Union reaffirmed that food products from cows treated with rbST are safe for human consumption, and they recommended the approval of two rbST products based upon their review of all aspects of safety and effectiveness.