 Each year some 1.6 billion drug prescriptions are filled in the United States about seven prescriptions for every man woman and child The job of the Food and Drug Administration is to make sure that when they are used properly these drugs are safe and they work The title of this program is FDA approved We'll look at how the pharmaceutical industry develops a new drug and how FDA decides when a drug is safe and effective It takes about 10 years and 125 million dollars to get an important new drug on the market Most of this time is spent by the manufacturer in testing FDA spends about two years reviewing the test results The drug industry thinks it takes too long to get a drug approved and onto the market on the other hand Consumer groups often complain that FDA approves drugs too quickly and without adequate testing So FDA is caught in the middle and that is as it should be Never has FDA felt the pressure more than it does today for the AIDS epidemic and technological breakthroughs such as gene splicing have raised the voices of those demanding swift approval of safe drugs in View of these pressures ten years to get a new drug on the market seems like a long time and it is But as we shall see FDA controls only a relatively short segment of the development period And FDA puts the most important drugs on a fast track for review to save time and lives In our look at developing drugs that are safe and effective Let's start with definitions of those two words We'll also look at what FDA does and what manufacturers must do to live up to those definitions Safe means the drugs risks and side effects are acceptable in relation to its benefits Effective means a drug does what the manufacturer claims it will do FDA does not develop drugs nor does it test drugs for approval although the agency may call for tests to be made Coming up with new drugs and testing them are the responsibilities of drug manufacturers The drug development process is complex and time-consuming It encompasses work in diverse fields including organic chemistry physiology statistics biochemistry molecular biology toxicology pharmacology and computer science The process begins with basic research scientific sleuthing Screening large numbers of compounds Scientists look for signs of biological activity that may prove beneficial Industry experts estimate that only one of every 2,000 chemicals and compounds studied ever reach consumers In laboratory studies researchers add compounds to cell cultures enzymes or cellular substances to find which show a desirable effect Once scientists find a chemical that shows some biological activity in test tube studies They analyze its structure and prepare it for tests in animals In animal tests short-term toxicology tests show whether a potential drug has toxic side effects and indicate the safe dosage range Compounds that are ineffective or too toxic are given up at this stage of development Drug companies make every effort to use as few animals as possible and to ensure their humane and proper care Occasionally a compound that has failed to work on one disease is found later to work on another Such was the case with Zadavudin also known as retrovir and AZT the first drug approved for treatment of AIDS AZT was developed in 1964 as an anti-cancer drug, but it showed little promise in test animals During the search for a treatment for AIDS Retrovir was tried again and showed very positive results in human testing It was approved by FDA in 1987 after less than four months of review If no undue toxicity is discovered during animal testing the manufacturer or sponsor Files a notice of claimed investigational exemption for a new drug an IND The IND is a request to FDA for permission to conduct tests on humans to find out whether a drug is really Useful in treating disease the human tests are known as clinical trials in the IND The sponsor proposes a plan for conducting clinical trials FDA requires that study plans include sound statistical methods and a suitable basis for choosing test subjects That the researchers are scientifically qualified to do the study and that adequate safeguards exist to protect participants Further FDA requires that the trial designs permit valid comparison of groups given the drug and those not given it And that data be collected and organized appropriately FDA has 30 days to decide whether the drug appears to be safe enough to test in humans and that the trial plan makes scientific sense Clinical trials are conducted by physicians working in university or government medical centers or in private practice The trials are financed by the drug manufacturers or by the national institutes of health Data from clinical trials conducted in foreign countries may be accepted by FDA as long as those studies meet the same standards that apply in the United States Normally clinical trials are carried out in three phases that involve progressively larger numbers of people Phase one testing involves a small number of healthy volunteers often 100 or less who receive the drug for a few days It takes about six to eight months to complete these tests Phase one is designed to study the safety of the drug how it's absorbed Processed and excreted by the human body what effects it has on various organs and tissues and what side effects occur This provides essential information about how much of the drug an actual patient should receive How often it should be used and what safety precautions are needed Of every 20 drugs for which companies seek FDA approval to test in humans only about 13 or 14 successfully complete phase one trials and go on to phase two Phase two studies involve up to several hundred patients who have the disease Or condition for which the drug is intended These studies show whether the drug is effective and whether there are any side effects and risks for people after a short period of use Most phase two studies are randomized controlled trials That is a treatment group receives the drug while a control group similar in age sex and disease state Receives either standard treatment for the disease or a placebo Often phase two studies are double-blind Neither the patients nor the researchers know who is getting the experimental drug Of every 20 experimental drugs only about seven survive phase two to go into phase three testing Phase three clinical trials can involve several thousand patients and may continue for three to four years or longer These long-term phase three trials provide extensive verification of a drug's safety and effectiveness in treating disease They help disclose less common side effects and provide more information about optimum dosage Of every 20 drugs that are considered for clinical trials only five or six survive all three phases of testing About four are eventually approved for marketing It is possible that the evidence of safety and effectiveness coming out of phase two studies could be so strong that phase three trials would not be needed Such was the case with the AIDS drug retrovir During the four to six month period of phase two testing Only one AIDS patient died while being treated with retrovir while 19 died while being given a placebo When human testing is completed the sponsor prepares a new drug application or NDA The NDA describes the drug's composition and toxicology its behavior in the body The results of all testing and how the drug is manufactured processed and packaged An NDA may reach several thousand pages in length giving FDA a time-consuming review task Often delays result because NDAs leave questions unanswered, are poorly organized or are otherwise inadequate for timely review and approval During the NDA review FDA may contact the sponsor to discuss problems If there are major deficiencies in the NDA substantially more work by the sponsor may be needed The opinions of experts both within FDA and outside the agency go into the decision to approve a drug FDA also uses advisory committees composed of experts from outside the agency to help evaluate test results and other NDA data FDA approves about 20 to 25 totally new drugs for marketing in the united states each year Along with about 500 requests for new dosage forms and duplicate products of older drugs The order in which FDA reviews NDAs is determined by a classification system that gives priority to drugs with the greatest potential benefit FDA is taking a number of steps to simplify and expedite the drug review process The agency has streamlined its regulations and issued guidelines to help sponsors plan better clinical trials and prepare shorter clearer NDAs The agency also is inviting sponsors to submit data in electronic formats And new regulations allow broader use of promising experimental drugs such as retrovir Indesperately ill and dying patients years earlier than was previously possible FDA approves all the information that can be used on labels for the drugs package inserts and pharmacological reference materials This includes a comprehensive description of the drug's chemical composition Pharmacology indications for use contraindications or when it should not be used and possible side effects All this information won't be found on the label of the drug package that the patient sees But it must be included in packaging and materials supplied to doctors and pharmacists The drug development and approval process isn't perfect Even after rigorous trials and extensive review drugs are sometimes found to cause unexpected problems after they've been on the market for a while Physicians and drug firms report any incidents of unexpected side effects to FDA Based on these reports, FDA may require firms to change drug labeling to include new warnings or occasionally to remove a drug from the market For physicians and other health care providers ads placed in professional journals and direct mail brochures are major sources of information about prescription drugs FDA regulates advertising for prescription drugs The law requires that drug information be truthful fully informative and fairly balanced Whenever material is found to be false or misleading FDA requires the manufacturer to place corrective ads in these same journals Or to send corrective letters to physicians This is the drug approval process from its chemical beginning to how a drug is advertised once it gets on the market It is a delicate balancing act always weighing risks against health benefits for all of us