Amyotrophic Lateral Sclerosis or “ALS” is a neuron disease that affects over six thousand (6,000) Americans every year and currently has no cure (Festoff 4). The disease is rare but can affect anyone because there are no racial, geographic or genetic barriers to the disease. Recently, Steve Gleason was diagnosed with ALS and said “Because ALS is underfunded, patients have had no option but to fade away and die. That is not OK.” (CBSsports 1). Recently, a company created Genervon, which is a drug that claims to be able to treat ALS. This drug has created a lot of debate because the Food and Drug Association (“FDA”) did not approve it, but the European Medicine Agency (“EMA”) has. This begs the questions - - does the FDA have a reason to be withholding this potentially life-saving drug from patients who essentially have no hope already and, if so, what is the reason? The FDA recently released a statement about Genervon. The statement created significant controversy because the FDA did not release the reason why the drug has not been approved. Instead, the FDA only asked the company responsible for Genervon to release all the data from a recent trial. This statement devastated thousands of people with ALS because the FDA’s statement signals that it is still far from approving the drug. Ultimately, this begs the question - - is the FDA saving or ending lives by not releasing this drug? For the FDA to be effective, it must have the perfect balance of speed and safety. It is crucial for the FDA to get medicine out quickly because it is uncertain how much longer somebody has to live but it is also important to ensure that the medicine is safe for use. In many cases, the FDA has to choose whether it is going to approve a drug quickly or hold it longer for further examination. In these situations, the FDA needs to value safety higher than speed. It is true that the extra time taken to approve a new drug can cause some to pass away, but it is more important to fully ensure that it is safe for use. The FDA needs to reexamine its 510(k) approval process because it is currently too expedited and not safe.  The FDA also needs to implement a policy of complete transparency with regard to clinical trials to ensure the safety of Americans.

The FDA uses a scientifically based process to determine the safety and efficacy of experimental drugs (fda.gov 1). The FDA approval process involves identifying the class of a drug. Based on the class, it goes through one of three approval processes. There are only three types of classes for the drugs. The first class involves the lowest risk while the third class involves the highest risk (jamanetwork.com 1). The three different types of approval processes are no FDA review, the 510(k) process and the rigorous PMA process. The PMA process is by far the most stringent of the three. The 510(k) is supposedly similar to the PMA process, but it is more expedited because the drug being tested is expected to be relatively low risk.

Once the approval process to be applied is selected, the FDA approves drugs by doing three or occasionally four stages of trials (fda.gov 1). The first stage of trials is used to determine dosing, how the drug is metabolized and excreted, and to identify the possible side effects (fda.gov 1). This is generally the smallest of the trials with between twenty (20) and eighty (80) volunteers. Of these volunteers, some have the disease and some do not (fda.gov 2). The second stage of trials involves between one hundred (100) and three hundred (300) participants who have the disease for which the medicine is being tested (fda.gov 2). This stage is used to attempt to ascertain if this drug is effective in treating those with the disease and gather additional safety data (fda.gov 2). If the stage two trials indicate that the drug may be effective and the risks are acceptable, the drug moves on to the next phase of trials (fda.gov 2). In the third stage of trials, the drug is tested with between one thousand (1,000) and three thousand (3,000) people with the disease (fda.gov 2). This stage of trials is used to further test whether the drug is effective or not, monitor the side effects, and, if available, compare its effects to a standard treatment (fda.gov 2). The fourth stage of trials is hardly ever used and, when it is, it is after the drug has been approved and on the market (fda.gov 2). The amount of people in this stage of trials varies and is used to learn more about long-term risks, benefits and to test the product in different populations of people (Miller 1). 

In January of 2004, the United States Government of Accountability Office published a critical article of the 510(k) process and the FDA requested that the Institute of Medicine conduct an independent outside review (Zuckerman, Brown, Nissen 3). From this review, in August 2004, the FDA released an internal report that indicated that several changes were made to the approval process (Zuckerman, Brown, Nissen 4). Following the report, Dr. Zuckerman, from the National Research Center for Women and Families, did an experiment to examine the effectiveness of the FDA approval processes. The experiment sought to examine which approval processes were responsible for the majority of Class One recalls, which the FDA defines as the highest risk (Zuckerman, Brown, Nissen 7). From January 2005 to December 2009, there were one hundred thirteen (113) Class One recalls. Upon further examination, the PMA process was used to approve only twenty-one (21) (19%) of the one hundred thirteen (113) devices listed as high-risk recalls that could cause serious health problems or death. Eight (8) (7%) were completely exempt from FDA regulation and were merely registered with the FDA and four (4) (4%) were counterfeit devices or categorized as “other” and did not go through any of the three (3) processes for approval, clearance, or registration (Zuckerman, Brown, Nissen 7). Eighty (80) (71%) were cleared through the 510(k) process, showing this process caused the clear majority of recalls. This experiment clearly shows that although the FDA made several changes to the 510(k) process, not nearly enough was done. The 510(k) process led to over seventy percent (70%) of Class One recalls.  It is hard for the FDA to ignore that the 510(k) review clearly causes the majority of recalls. The FDA needs to adjust the 510(k) process to make it more like the PMA process, in that it needs to be longer and more stringent. However, it also needs to ensure that low risk drugs are being approved and brought to the public quickly. Although the FDA’s first attempt at fixing this process failed, if it is able to make the process more stringent without making the process take too long, this is a small process change that the FDA can implement to significantly reduce the risks and recalls of drugs, while continuing to approve drugs quickly. 

The FDA is generally only in charge of ensuring the safety of the United States while the EMA is in charge of all twenty-eight (28) countries in Europe. The EMA was formed in 1995.  The EMA is a relatively new organization when compared to the FDA, which was formed in 1938 (fda.gov 3). In its short existence, the EMA has been able to centralize the agency so all twenty-eight (28) countries are able to work together. The FDA and EMA have similar approval processes. However, the big difference between the two is that the EMA is much slower to approve new medicines. On average, it takes the EMA four hundred ten (410) days to get through the three clinical trials while it only takes the FDA half that time (Carroll 1). In a recent study, researchers sought to compare and contrast how the FDA, EMA and Health Canada approved new cancer drugs. In this study, the FDA was by far the fastest to approve new drugs, but also had the highest number of drugs that needed to be put through the fourth stage of trials to readjust the dosages and ensure their safety (Samuel and Verma 2-3). This experiment is further evidence that although the FDA is the fastest to approve new drugs, it also has by far the greatest number of recalls.

In October of 2016, the EMA published the clinical trial reports of two new drugs - - carfilzomib and lesinurad (Davis and Miller 1). By doing so, the EMA enabled access to nearly two hundred sixty thousand (260,000) pages of “detailed clinical trial information, including protocol, statistical analysis, and detailed clinical data” (Davis and Miller 1). From these studies, the EMA only considered two pages to contain “Confidential commercial information” (Davis and Miller 1). This was the first time any organizations responsible for testing and regulating drugs released this amount of information. In 2014, the EMA announced that it would be adopting policy No. 0070. This policy allowed for the online publication of all clinical studies in connection with a marketing authorization application submitted after January 1, 2015, regardless of whether the application was accepted, rejected or withdrawn. (Davis and Miller 2). 

The EMA decided to adopt this new policy to achieve the goals of “better informed use of medicines” and “to make medicine development more efficient” by helping researchers to access data from past trials (Davis and Miller 3).  On his first day in office, former President Barack Obama sought to create an unprecedented level of openness in the government (Hamburg and Sharfstein 1). Essentially, President Obama wanted the FDA to adopt a policy similar to that of the EMA by being completely transparent in its findings. The FDA claims to have embraced this and announced a transparency initiative. This initiative was a start to fixing the problem of transparency at the FDA but was not nearly enough. The FDA still does not disclose whether a drug or device is under development, when an application is withdrawn by a sponsor, whether the agency has placed a hold on clinical studies, whether it agrees with reports published by others about products with pending applications not yet approved by the FDA, and why it does not approve a marketing application (Hamburg and Sharfstein 4). This leaves huge gaps in information that the public needs to know. A perfect example of this is Genervon. The FDA will not release why it has been approved by the EMA but has not been approved by the FDA. Additionally, it is unclear whether Genervon is being placed on hold in the approval process or if the company has simply withdrawn the application. For people with incredibly limited time because of a life-threatening disease, this lack of information must be infuriating. By not releasing this information, the FDA is causing more stress in the lives of those affected with diseases who desperately need medicine. Moreover, when the FDA is not completely transparent about its findings, it leads to a major public relations problem because people want to know all known risks before they take medicines.  The FDA needs to be completely transparent with its findings because when it does not release vital information, it leads the public to distrust the FDA. In contrast, by sharing its findings, the FDA is able to better inform the public of potential risks of taking a drug. In addition, it would be an incredible help to researchers because they would be able to quickly access past clinical trials and examine how other drugs succeeded or failed. 

Those opposed to changing the 510(k) process would argue that the FDA and all other institutions of a similar nature acknowledge that those with illnesses need to be treated quickly and effectively. According to a recent study, the FDA is much faster than other institutions at supplying medicine. The FDA was able to give approvals for new medicines in one hundred eighty-four (184) days. In comparison, it took the EMA almost twice as long to approve the same medicines (Roberts, Allen Sigal 5). In that regard, the FDA is much more efficient than other agencies. The FDA acknowledges that for many people, even just one day can be the difference between life and death. Those opposed to changing the 510(k) process would argue that it is more important to get medicine out to the public quickly because in many cases there is no cure, so any potential treatment is worth the risk.

From past experiments, it is clear that the FDA does a far better job at getting medicine to those in need than other agencies around the world. However, the FDA needs to work on its 510(k) process because too many medicines are approved and then subsequently recalled. Additionally, the FDA defends its current policy of not releasing certain information to the public based upon two major pharmaceutical companies that have sued the EMA for information it released. Those who are against the FDA being transparent about its findings assert that people would be hesitant to take a medicine knowing it originally was rejected or is approved, but has massive side effects in a very small number of people.  Others claim it is actually better for patients to have all possible information before choosing to take a drug.

As criticized as the FDA is, it is still widely considered to be the global leader in drug evaluation and regulation. In comparison to the EMA and Health Canada, the FDA is much more effective and able to get medicine to the public in half the time it takes the EMA and Health Canada. However, the FDA struggles with being safe. This is clearly demonstrated by the FDA having a significantly greater amount of recalls than the EMA and Health Canada.

The FDA acknowledges that for it to be completely effective, the FDA must have a perfect balance of speed and safety. I believe that the FDA should change the 510(k) approval process to make it longer and more stringent; thus making it similar to the PMA approval process. By doing this, the FDA is still able to approve drugs quickly and safely through a 510(k) approval process for three drugs that are not considered to be high risk. The ultimate goal of the FDA should be to limit the number of recalls and ensure the drugs it does approve are truly safe for use. Additionally, the FDA should adopt a similar policy to the Num. 0070, which was adopted by the EMA and led to outright transparency in the EMA’s findings. By doing this, the FDA would be able to better educate the public on risks involved with taking certain drugs and help researchers by publishing past clinical trials. Adjusting the 510(k) approval process and implementing a policy of complete transparency certainly would not solve all of the FDA’s problems but it would definitely be a step in the right direction. 
