Food and Drug Administration Approval - Literature review Example

Food and Drug Administration Approval The Food and Drug Administration (FDA) the main body that is accountable for ensuring that any foods, cosmetics, medical devices and medicines available to the public are safe to use and work at a maximum efficiency (FDA, 2010). In total, the FDA is accountable for products worth in total over one trillion dollars every year (Lipsky and Sharp, 2001). To maximise efficiency of this, there are several centres that the FDA is the head of and these are the Center for Food Safety and Applied Nutrition (CFSAN), the Centre for Veterinary Medicine (CVM), the Centre for Devices and Radiological Health (CDRH), the Centre for Drug Evaluation and Research (CDER) and the Center for Biologics Evaluation and Research (CBER). Of these, it is the CDER that responsible for making sure that all the drugs that are approved are safe for use and do not have any adverse effects (Gaylor et al, 1997). Despite strict regulations that govern the approval of drugs, the FDA still faces a lot of distrust from the public and criticism that the drug approval process is not stringent enough. This issue will be discussed further in this paper by taking a look at the clinical testing that takes place before a drug is approved for public use, the follow-up following it’s approval and some examples of drugs that have unfortunately had to be withdrawn. To fully appreciate the role of the FDA in the production of a new drug, it is important to take a close look at the FDA’s approval process for new drugs. There is generally a preliminary stage where a new drug application is made to the FDA. A test is done using the drugs in live animals, usually rodents. This usually takes about 3-4 years to complete. Following this, it is followed by either 3 or 4 phases of testing by the FDA before approval (Lipsky and Sharp, 2001). Each phase must be successful before moving on to the next. These phases are described briefly below. 1) Clinical evaluation, phase 1 20 to 100 volunteers are generally used as the testing group. This phase takes a look at the pharmacologic actions of the drug and records data on how it is used in the body during the time it is present (Lipsky and Sharp, 2001). 2) Clinical evaluation, phase 2 100-300 people who suffer from the condition the drug is made for are the testing group. This phase mainly looks at whether the drug is actually effective in treating the medical condition. Sometimes, studies in animals as well as in humans are done at the same time (Lipsky and Sharp, 2001). 3) Clinical evaluation phase 3 The testing group for this phase usually are thousands of people living in different places. Testing is done by clinical doctors who treat patients with the condition (Lipsky and Sharp, 2001). Surprisingly, only 10%of drugs usually make it through phase 3 of testing. To make it through these phases, they must exhibit no adverse effects. Adverse side effects have been defined as ‘an appreciably harmful or unpleasant reaction, resulting from an intervention related to the use of a medicinal product, which predicts hazard from future administration and warrants prevention or specific treatment, or alteration of the dosage regimen, or withdrawal of the product’ (Edwards and Aronson, 2000). If the drugs do make it through phase 3, in some cases, there may be a clinical evaluation phase 4 or post marketing studies that are done too. These are done while the drug is being used by the general public to make sure that there are no ill effects as was seen in phases 1 to 3. The entire process of clinical evaluation may take between 8-12 years is on average 1 of every 5000-10000 drugs that are submitted for approval to the FDA, that make it past this stage and get approval (Lipsky and Sharp, 2001) . However, in cases where drugs are needed to deal with life threatening conditions that progress very fast, such as human immodeficiency virus, there is a fast track process which involves clinical testing on terminally ill patients (Lipsky and Sharp, 2001). Even after carrying out these four phases of testing, the FDA still faces a lot of criticism. A main reason for criticism of the FDA is that it appears to favour extremely development strategies that are free of risk which can mean that some drugs have practically no chance of making it very far in the testing phases. These safe approaches accepted by the FDA can include making subtle changes to already approved drugs, the use of agent that have already been approved and many other such factors. This attitude has led to several drugs being developed for a few specific conditions where as other such as Alzheimer’s are largely ignored. It had been said that this is mainly because the FDA makes it almost impossible to put together a plan that shows that a drug would prevent rather than reduces the symptoms displayed by sufferers of Alzheimer’s (Wood, 2006) It has also been said to be because the requirements of the FDA are sometimes too narrow. This is well seen in the example of the drug that was used to control appetite was dexfenfluramine (Redux). The phases of approval showed that women who took this drug lost on average of 6 pounds and this was seen as essential in controlling the growing problem of obesity in the United States. What the FDA failed to take into account was that this drug, in addition to helping with weight loss, also played a part in pulmonary hypertension even though evidence to suggest this was available. In addition to pulmonary hypertension, a side-effect that was unexpected also was seen which was cardiac valvulopathy and this led to the drug being recalled in its first year of use (Avorn, 2005). Considering the cost of developing a single drug which may run up to 500 million dollars (Lipsky and Sharp, 2001) according to some estimates it is unacceptable that the FDA is approving drugs such as dexfenfluramine without considering other effects of it rather the target effect. Another case where the FDA was considered to be biased in its decisions was in the drug terfenadine which was only withdrawn from the market once a substitute had been found for it rather than when adverse effects were first reported (Wood, 1999). Another example in which the FDA came under intense scrutiny was in the case of the drug Bidil which the FDA approved in 2005. This drug is used to treat heart failure and the controversy was that it was only approved to treat black people. The FDA indicated that in their clinical studies, there was little or no effect seen in other ethnicities while there was a marked improvement seen in black people. Critics of this decision have argued that there was insufficient evidence to suggest this and that the fact that the FDA approved the drug for use in black was not based on sound scientific reasoning, but rather just by looking at race. It has been suggested that a further clinical study was needed to fully appreciate the effect Bidil but in reality, another clinical trial would have taken years and many years and a lot of people would have died waiting for approval of the drug by the FDA. Many have even said that this was a commercial ploy by the FDA to get this drug approved. It must be said that while people have been outspoken in this case, many of them fail to take in to account that two clinical trials were carried out in which there was little or no effect seen in white patients and a third one showed an impressive improvement of 43% in blacks. There are another group of people, however, who defend the FDAs decision and maintain it was only right that they provide access to drugs to at least one racial group in cases where the condition might be life threatening (Temple and Stockbridge, 2007). In light of cases like these, there have been calls for reforms to the FDA. There have been suggestions that the FDA should be privatised. This may increase the amount of resources it has available to make sure that clinical testing is done efficiently. Resources are a major cause of concern for the FDA due to the vast number of drugs that are submitted for approval (Rutherford, 1995). Another suggestion has been to create a separate body that is responsible for looking at safety in phase 4 of trials, that is after the drug has been approved by the FDA and is available the public. This is mainly because having a separate organization would mean there is less conflict of interest and objectivity will be maintained. This has worked well in other fields such as in the aviation industry (Wood et al, 1998). In conclusion, it can be said that the FDA does indeed have stringent methods in place for the approval of a new drug. There are three clinical phases to this approval process followed by stage 4 post-marketing. This entire process takes up to 12 years, at a cost of approximately 500 million and surprisingly only 1 out of every 5000-10000 drugs is actually approved for use in the general population. Despite all these regulations, the FDA has in the past approved drugs that had to withdrawn due to their many adverse effects dexfenfluramine . Also, the FDA faces criticism for not carrying out testing that is stringent enough, mainly due to a lack of resources. This was seen in the case of Bidil. It can be said that while the FDA does actually carry out strict testing of all drugs, it needs to find a method where by drug approval includes looking at all effects of a drug rather than just the target effect. In addition, a method to try and make the drug approval process faster would be very helpful too as many people can die waiting for drugs to be approved. Bibliography Avorn, J. (2005). FDA standards-good enough for government work?. The New England Journal of Medicine. 353 (10). Pp 969-972. Edwards, I.R and Aronson, J.K. (2000). Adverse drug reactions :definitions, diagnosis, and management. The Lancet.356. Pp 1255-1259. FDA (2010). Retrieved from http://www.fda.gov/AboutFDA/CentersOffices/default.htm. Gaylor, D.W.; Axelrad, J.A.;Brown, R.P.; Cavagnaro, J.A.; Cyr, W.H.; Hulebak, K.L.; Lorentzen, R.J; Miller, M.A; Mulligan, L.T and Schwetz, B.A. (1997). Health Risk Assessment Practices in the US Food and Drug Administration. Regulatory Toxicology and Pharmacology. 26. Pp 307-321. Lipsky, M.S. and Sharp, L.K. (2001). From Idea to Market: The Drug Approval Process. Journal of American Board of Family Practices. 14. Pp 362-367. Rutherford, E.M. (1995). The FDA and privatisation – The Drug approval Process. 50 Food and Drug. The Lancet. 356. pp 1255–59. Temple, R and Stockbridge, N.L. (2007). BiDil for Heart Failure in Black Patients: The U.S. Food and Drug Administration Perspective. Annals of Internal Medicine. 146. Pp 57-62. Wood, A.J.J.; Stein, M.C. and Woosley, R. Making Medicines Safer-The need for an Independent Drug Safety Board. The New England Journal of Medicine. 119.pp 1851-1854. Wood,A.J.J. (2006). A Proposal for Radical Changes in the Drug Approval Process. The New England Journal of Medicine. 355(6). Pp 618-623. Wood, A.J.J. (1999). The Safety of New Medicines. Journal of American Medical Association. 281 (18). Pp 1753-175. Read More