Tag: FDA

Intentional Genomic Alterations: A New Development in Animal Biotechnology

The livestock industry relies on traditional breeding methods for desired traits, but this is costly and limits which animals can be bred. Intentional Genomic Alterations (IGAs) are being developed in animals to give desired traits faster. IGAs make targeted and random DNA sequence changes to an animal’s genomic DNA. This is especially helpful for the livestock industry because traditional breeding methods only give traits to offspring, but IGAs can give traits to an entire generation at once. Scientists found a gene called PRLR that, when altered, creates short, slick hair in cattle, more commonly referred to as SLICK. SLICK enhances heat stress tolerance and reduces disease susceptibility. This is especially useful for cattle farms in tropical climates because heat stress can affect milk yield and fertility. There are three cattle breeds with SLICK in the United States and Brazil. The Food and Drug Administration (FDA) approved SLICK cattle as safe for human consumption in 2022. 

The FDA regulates IGAs in animals by reviewing the product claim, how the IGA was produced and introduced to the animal, the characteristics given to the animal, the animal’s health, the durability of the desired effect, the environmental impact, whether it is safe for human consumption, and the effectiveness of the IGA. In May 2024, the FDA announced it would be collaborating with the EPA and USDA to ensure sustainability and safety in the biotechnology of IGAs. IGAs are being developed for uses other than for the livestock industry, including: biopharmaceuticals, research, xenotransplantation, therapies in companion animals, disease resistance, and food supply. There have already been drugs from IGAs approved by the FDA. A recombinant anti-thrombin drug was developed from the milk of transgenic goats. To create the drug, human DNA is inserted into the cells of goats and excreted from the offspring’s milk. The drug is in clinical trials and, if successful, will be more cost-effective than current drugs on the market for coagulation disorders.

Some IGAs are still in the developmental stage. Revivicor is a xenotransplantation company aiming to make pig kidneys and hearts viable for human transplant. Organs from another animal will be rejected by the body immediately upon implantation, but Revivicor is using IGAs to combat organ rejection. There are 10 genes in the pig genome that are edited through mutation and by adding human genes. 

Despite the benefits that IGAs may bring, there are ethical concerns for animal welfare. Making IGAs is inherently invasive and subjects the animals to surgeries, tissue sampling, and possible complications resulting in disability or death. IGAs are still in the conception stage and will have effects on the food supply, pets, pharmaceutical products, and other developments. There are areas of research of animals with IGAs that need more information, and there could be unanticipated results and concerns. For example, animal clones, copies of animals traditionally bred, have been limited recently because the offspring of the cloned animals developed varying abnormalities. Unforeseeable results are possible; however, the most recent development in IGA information is a new approval process for heritable IGAs released by the FDA. There are two parts, the first part categorizes IGAs based on their risk. Higher-risk IGAs will need the FDA’s full approval. The second part provides a guide for developers of higher-risk IGAs by giving guidelines of what is needed for the FDA to evaluate the products. This new approval process is an important step towards regulating IGAs, but it also emphasizes the need for continued research and ethical consideration.

The FDA and Insulin: Biologic and Biosimilar Pricing

The United States is the most expensive market for biologic drugs, including insulin, despite initiatives devised by the Food and Drug Administration (FDA) and the Affordable Care Act. For more than a decade, the biosimilars market in the US has lagged behind the European market, whose medicines are as much as 80 percent cheaper. The Biologics Price Competition and Innovation Act (BPCIA), a provision in the 2010 Affordable Care Act, authorized the FDA to create a new regulatory scheme to approve biosimilars, which are products designed to work like biologics that have already been licensed. In 2015, the FDA approved the first biosimilar, Basaglar (a type of insulin), and by 2017, there were three marketed biosimilars and two more that had been approved. The development of biosimilars is intended to increase competition among biologic manufacturers and drive down prices and making products like insulin more accessible.

Despite the BPCIA and approval of biosimilars like Basaglar, the cost of insulin has continued to skyrocket, and the FDA proposed a new classification system to address soaring prices. In December, FDA Commissioner Scott Gottlieb unveiled a plan to classify insulin as a biologic as opposed to its previous classification as a drug. In doing so, biosimilar drug makers will be enabled to develop biosimilars that can be substituted for the original biologic. Although Gottlieb’s proposal will likely not go into effect until March 2020, the new classification scheme could create competition in what is currently a limited marketplace of insulin, thus driving down the cost for the millions of Americans with diabetes.

As of now, the insulin market is dominated by three manufacturers: Sanofi, Novo Nordisk, and Eli Lilly. Due to their market dominance, these three companies have driven up the cost of insulin, which has tripled between 2002 and 2013 and doubled between 2012 and 2016. Sanofi, Novo Nordisk, and Eli Lilly have faced immense scrutiny due to the price hikes, and criticism peaked when Minnesota Attorney General Lori Swanson filed a legal salvo against the manufactures for their “deceptive” practices. With the issue of insulin pricing entering the public eye, it is clear changes must be made.

Gottlieb’s proposal, designed to implement the intent of Congress, will address pricing standards in three ways. The first step is to extend the anti-evergreening provisions, which are meant to prevent manufacturers from having exclusivity and forestalling competition, to the newly deemed biologics and biosimilars. The next step is to address patent exclusivity and to stop twelve years of exclusivity once the current terms expire. Lastly, the proposal intends to offer guidance to current manufacturers when they submit a New Drug Application for approval under the Food, Drug, & Cosmetic Act (FDCA). This guidance will offer standards for transitioning a product from the drug pathway to the biologic pathway so that it meets the requirements of the Public Health Safety Act and section 505 of the FDCA. With these changes afoot, the FDA and Congress will hopefully make strides in addressing the current high cost of insulin and allow for new biosimilar manufacturers to enter the market, thus significantly benefitting the millions of Americans with diabetes.

Labelling It Healthy

What does the word “healthy” mean? The word is almost ubiquitous and is on every food, drink, or clothing label. However, there is little consensus on what the word “healthy” actually means. Does “healthy” mean low fat, low sugar, and low salt? While the word will likely still be used to describe a list full of foods and drinks, the Food and Drug Administration (FDA) is planning to create some clarity and redefine the word. FDA published a Federal Register (FR) notice announcing that the agency will be receiving information and comments on the use of the term “healthy” in the labeling of human food products. Currently, the FDA defines the term “healthy” when used as an implied nutrient content claim in labeling human food products at 21 C.F.R. §101.65(d)(2).

The FR notice comes a year after the FDA’s Center for Food Safety and Nutrition (CFSAN) issued a Warning Letter to KIND LLC, a producer of ‘Kind’ bars and other fruit and nut snacks, because the labels and labeling of KIND’s nutrition bars bore a variety of nutrient content claims, including “healthy,” but the products did not meet the requirements to make such claims.  KIND LLC subsequently sent a citizen petition to the FDA Commissioner requesting that the FDA update the FDA’s existing requirements related to food labeling to become consistent with current federal dietary guidance as set forth in the 2010 Dietary Guidelines for Americans and with the latest scientific evidence discussed in the Scientific Report of the 2015 Dietary Guidelines Advisory Committee (2015 DGAC Report).

As stated in KIND LLC’s letter to the FDA, the FDA’s current regulatory approach for food labelling is inconsistent with the DGAC recommendations. With obesity rates in the United States continually increasing at alarming rates, educating consumers about how to carry out a “healthful” diet is essential to public health. KIND LLC requested in the letter that the FDA take a holistic approach when reviewing the healthfulness of foods, instead of identifying and demonizing one food ingredient or nutrient.

The health label on packaging is an easy, but possibly misleading, tool that food companies can use to help educate consumers and give them easily accessible information about the food that they choose. A food may be low in salt, sugar and/or fat, but it doesn’t mean that it has the nutrients to create a healthful diet, which is why it is so important for the FDA to properly address this issue. It is likely that there will be an increase in regulation or scrutiny around food labels in order to create a more transparent food system, as well as attempt to stifle the upward trend of obesity.

The End of Antibiotics?

Antibiotic resistance is upon us and affects both human and animal health. In a May 2016 report commissioned by United Kingdom (UK) Prime Minister David Cameron, Jim O’Neil, economist most widely known for coining the term BRICs for the emerging economies of Brazil, Russia, India and China and Commercial Secretary to Her Majesty’s Treasury in the UK, pointed out that 700,000 people each year die from bacterial infections that do not respond to antibiotics, and even more recently a new National Academy of Medicine (NAM) paper, conducted by six experts, outlines the evidence that there is a connection between antibiotic use in food animals and antibiotic resistance in people.

For almost fifty years, antibiotics have been approved for use in animal agriculture and human medicine to treat illness, and they have had a remarkable impact on our ability to improve the health of humans and animals alike. However, there are real concerns about the overuse of antibiotics in human and animal medicine, specifically as it relates to the development of antibiotic-resistant strains of bacteria in the US and around the world. The use of antibiotics has been the center of discussion in the US, European Union (EU), and other public forums, such as the World Economic Forum (WEF). In September 2016, there will be a United Nations high-level meeting on antimicrobial resistance at the General Assembly in New York. Global leaders will meet to commit to leading the fight against antimicrobial resistance. The EU has even proposed to include an article on Anti-Microbial Resistance within the SPS Chapter of the Trans-Atlantic Trade and Investment Partnership (TTIP), a trade agreement between the US and EU representing more than forty percent of global trade, addressing steps to mitigate resistance.

In recent years, the animal agriculture industry has placed a high importance on antibiotic stewardship to ensure these critical drugs continue to be effective at fighting bacterial diseases. The Food and Drug Administration (FDA) has issued guidance on the use of antibiotics in food-producing animals, with the goal to phase out the use of antibiotics for growth promotion. All of the affected drug sponsors have committed in writing to making the changes described in the guidance by the end of 2016. Additionally, the FDA wants to ensure the judicious use of antibiotics when used to treat and prevent animal diseases by requiring that antibiotics be administered under the supervision of a veterinarian.

Even with the changes made by the FDA and industry, there is a call to introduce legislation that would more stringently regulate the use of antibiotics in animal agriculture and allow only the use of antibiotics to treat illnesses and not for prevention. California passed the first law in the nation in October 2015 that will require a veterinarian’s prescription for therapeutic antibiotic uses in livestock, ban other uses (including low-dosage levels used to prevent diseases), and require that data be collected on antibiotic use. With the issue on the global stage, it is possible that we will see more advances in both state and federal legislatures to regulate the use of antibiotics in either animal or human health.