IN THIS SUMMARY The United States Food and Drug Administration (FDA) has significant reach in the American economy, ranging from medicines and medical devices to items on the grocery store shelves. Since its inception in 1906, the agency has faced a variety of technical and political challenges. Looking ahead, the FDA faces many new demands that could enlarge the agency’s already expansive mandate. New responsibilities may include the cost of medicine, consumers’ pursuit of perfection through drugs, consumer lifestyles, tobacco, and counterterrorism. As the nature of public health changes over time, it is inevitable that the FDA’s scope and responsibilities will change as well. In Inside the FDA, Fran Hawthorne explains the history of the FDA, how its processes work, and what the future may hold for this government agency. SUBSCRIBE TODAY http://www.bizsum.com/summaries/inside-fda

2. INSIDE THE FDA The Business and Politics Behind the Drugs We Take and the Food We Eat AUTHOR: Fran Hawthorne PUBLISHER: John Wiley & Sons, Inc. DATE OF PUBLICATION: 2005 338 pages

3. FEATURES OF THE BOOK Inside the FDA is a comprehensive review of the agency’s history, responsibilities, stakeholders, and future.

4. THE BIG IDEA In Inside the FDA , Fran Hawthorne explains how the agency’s processes work, as well as how the agency interacts with different stakeholders.

5. INTRODUCTION The United States Food and Drug Administration (FDA) has significant reach in the American economy. Medicines and medical devices cannot be sold unless this organization deems that they are safe and effective. In addition, packaged foods cannot make health claims without approval from the FDA. Since its inception in 1906, the agency has faced a variety of technical and political challenges. In Inside the FDA , Fran Hawthorne explores the history of the FDA, how its processes work, and what the future may hold for the agency.

6. THE HISTORY OF THE FDA During the 1800s, no regulations existed for medicine or food. In 1862, Abraham Lincoln created the Department of Agriculture. Within this Department, Dr. Harvey W. Wiley headed the Bureau of Chemistry and championed the cause for food and drug safety. This Bureau was later reorganized and called the Food and Drug Administration. After publication of The Jungle by Upton Sinclair, Congress passed the Food and Drug Act of 1906—the first national legislation on food and medical safety.

7. THE HISTORY OF THE FDA Despite this law, poisonous medicines and unsafe food products continued to be sold. After 107 people were killed from an antibiotic, the Food, Drug, and Cosmetic Act of 1938 was implemented. This act created the framework for today’s FDA , requiring manufacturers to show scientific proof that their products are safe before they can be sold.

9. BRINGING A DRUG TO MARKET There are five basic steps a firm must take to move a drug from the laboratory to the marketplace in the United States: Preclinical trials . These consist of tests on animals. Investigational new drug application (IND) . This document describes the animal test results and the manufacturing process. It also explains the human testing plans in detail. Drug companies often schedule a pre-IND meeting with the FDA. The goal of this meeting is to discuss the specifics of the human testing plans. If companies can find out what the FDA wants in an IND, it is easier to write an application that will be approved.

10. BRINGING A DRUG TO MARKET Phase I clinical trials . Through testing on a small group of healthy volunteers, the company ensures the drug is safe. Phase II and III clinical trials . These are two progressively larger trials on humans who suffer from the target disease. The goal is to test both safety and effectiveness. Applications to sell the drug . After the Phase III clinical trials, companies must file either a biologics license application (BLA) or a new drug application (NDA). BLAs are used for drugs made from living materials (biologics) and NDAs are used for chemical-based drugs.

11. CLINICAL TRIALS AND NEW DRUG APPLICATIONS In recent years, several aspects of clinical trials have been debated: The use of placebos . Typical scientific practice provides only half of the test subjects with the drug being studied and the other half receives a placebo. However, placebos cannot be used if patients have life-threatening conditions. In the early 2000s, experts suggested that only a direct comparison of drugs can demonstrate that a newer and more expensive medication is better than an existing, more affordable version.

12. CLINICAL TRIALS AND NEW DRUG APPLICATIONS Drug dosages . The FDA encourages companies to experiment with a variety of drug dosages during clinical trials. However, if this introduces too much complexity, the agency may not insist. As a result, only high doses are usually tested because they are more likely to show strong results. Demographic groups . Until 1993, it was FDA policy to exclude women aged 14 to 50 from clinical trials, yet the individuals taking drugs are not all healthy men. In 1989, the FDA published guidelines for studying drugs in elderly populations and in 1993 issued similar guidelines for studies using both men and women.

13. NEW DRUG APPLICATIONS A new drug application is a company’s formal application for selling a drug. Every NDA contains every piece of information collected on every trial participant. It is common for an application to have between 100,000 and 200,000 pages, bound in several hundred volumes. An NDA is typically divided among several people at the FDA: a chemist, pharmacologist, statistician, toxicologist, perhaps a microbiologist, and the lead reviewer who is a medical doctor specializing in that type of drug. The reviewers are looking for two patterns in the application: (1) the side effects, deaths, and dropouts that point to safety, and (2) the progress of improvement in conditions that point to effectiveness.

14. NEW DRUG APPLICATIONS The FDA approves approximately 75 percent of NDAs. The other 25 percent meet three possible outcomes. In unusual cases, the FDA will not consider an application at all and will issue a “refusal to file” letter. Alternatively, the agency may reject an application based on Class 1 (minor problems) or Class 2 (major problems). The most common explanations for rejection are trials that were not conducted based on the protocol that had been planned with the FDA, unclear trial results, or trial results that show only a small improvement in patients. All drugs that are rejected can apply again, assuming that new tests produce better data.

15. THE FDA APPROVAL PROCESS The FDA changes the rules . The different divisions within the agency have reputations for being tougher or easier to deal with. The CDER is efficient, rule abiding, and consistently meets its user fee deadlines. The CBER is more academic, staffed by research scientists. The CDRH has the most lenient approval requirements, the smallest trials, and the quickest reviews. The agency does not understand the real world . Although most agree that the FDA employees are smart and dedicated, companies feel the staff does not understand business issues and the cost of developing a successful drug.

16. THE POWER OF THE PHARMACEUTICAL AND FOOD INDUSTRIES Both the pharmaceutical and food industries are very influential in Washington. Hawthorne writes that the FDA’s record for resisting industry influence is mixed. The agency has had better luck with pharmaceuticals than with food, but in general their stance has been too weak. In the 1970s, in response to complaints of long approval times, the FDA decided to communicate more openly with pharmaceutical companies. The belief was that more communication prior to applications being filed could contribute to drugs that followed the best procedures related to safety and efficiency. Once an application has been filed, however, it is too late for advice.

17. THE POWER OF THE PHARMACEUTICAL AND FOOD INDUSTRIES Another controversial interaction between the FDA and the pharmaceutical industry is when retired FDA employees go to work for pharmaceutical companies. The potential for conflicts of interest may arise long before retirement, as FDA reviewers consider taking a job in the industry at some future date. When it comes to influencing the FDA, larger pharmaceutical companies seem to have a better chance. Small biotech firms often have a hard time getting through the approval process, while large manufacturers that have submitted applications for many years can afford large government affairs departments.

18. THE CONSUMERS AND THE FDA As late as the early 1980s, the FDA did not view patients and consumers as stakeholders that the agency needed to answer to. However, the AIDS epidemic changed patient activism and affected the FDA approval process. AIDS activists helped spur the creation of treatment INDs and parallel track programs that hastened access to life-saving drugs. Patients also took on a greater role in the drug approval process, as patient or consumer representatives were added to FDA advisory committees. The goal was to get regulators to think about the human aspects of issues like dosage, safety, effectiveness, and scientific validity.

19. POLITICAL PRESSURES FACING THE FDA The FDA is undeniably subject to different political pressures . The Commissioner must be confirmed by the Senate and the agency’s funding must be approved each year by Congress. Traditionally, certain behaviors have been taboo when it comes to politics and the FDA. For instance, appointments to advisory committees are supposed to be based solely on scientific credentials. In addition, the FDA is not supposed to lobby Congress.

20. THE FDA, BIOLOGICAL PRODUCTS, AND RESEARCH Unlike chemical drugs, products made from living substances like human cells are more individualized and experience unexpected variations during production. Prior to 1972, biological products were regulated by the National Institutes of Health (NIH) until the Bureau of Biologics was created within the FDA. This organization eventually evolved into the Center for Biologics Evaluation and Research, which was distinct from the Center for Drug Evaluation and Research.

21. THE FDA, BIOLOGICAL PRODUCTS, AND RESEARCH In science, research can be divided into basic (or pure) research and applied research. Basic research explores questions about the fundamental mechanism of what is being studied, without a specific goal in mind. Applied research, in contrast, focuses on a practical result. At the FDA, employees engage in a regulatory form of applied research at both CDER and CBER. Drugs are becoming more complicated with the advent of genetic engineering, the decoding of the human genome, and other biotechnological techniques. As a result, many say it is essential that the CBER employees maintain their tradition of research.

22. DRUG ADVERTISING Each year, the pharmaceutical industry spends more than $3 billion on television and magazine ads. In May 1983, the first drug advertisement on television was broadcast. In response, the FDA asked pharmaceutical companies to comply with a temporary moratorium while it decided what actions to take. The FDA issued a ruling, stating that consumer ads for drugs had to follow similar rules to those in professional medical journals. They had to list all the side effects, instructions, conditions, and warnings that were in the package insert. Alternatively, companies could issue “reminder ads” that mentioned a drug by name, but did not say what the product did. In this case, the list of side effects could be omitted in a television ad.

23. THE FUTURE OF THE FDA Looking ahead, the FDA faces many new demands on its resources that could enlarge the agency’s already expansive mandate: The cost of medicine . Anything the FDA can do to move generics to market faster or to certify biologic generics would create a supply of less expensive drugs. Approving applications faster will save the industry time and money which should translate to lower prices. The FDA may want to incorporate a cost effectiveness analysis into the approval process. Consumers’ pursuit of perfection . If humanity-altering drugs are developed, the FDA may need to regulate drugs based on cultural values and ethical issues.

24. THE FUTURE OF THE FDA Consumers’ lifestyles . The FDA has not traditionally regulated how people live. However, the Center for Food Safety has identified obesity as one of its key issues. For some drugs with dangerous side effects, the FDA already dictates patient behavior concerning their use with birth control. Tobacco . The FDA has no authority over tobacco today, but cigarettes are dangerous to America’s health. If the FDA’s job is to protect and advance public health, the biggest single step it could take would be to regulate the product that is the number one cause of death in the U.S.

25. THE FUTURE OF THE FDA Fighting terrorism . To spur development of vaccines against bioterrorist agents, the FDA has eased up on the efficacy requirement. These vaccines are approved as long as they are safe in humans and effective in animals. The FDA is also looking at the food supply for deliberate acts of terror. As the nature of public health changes over time, it is inevitable that the FDA’s scope and responsibilities will change as well.

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