The FDA is Responsible for the Drug Shortages

The Food and Drug Administration (FDA) has implemented extremely restrictive drug policies that are generating drug shortages across the nation. According to the Regenexx blog, clinicians all over the United States have been feeling the effects of this pinch for some time.

Centeno gives the following example: “we were paying about $1 a bottle for local anesthetic, now when we can find it-that same bottle is often $4 a bottle.” As you might guess, this is having a significant effect on patient care, since surgery centers cannot get their hands on certain drugs. Cancer patients have been dramatically affected, since stocks of cheap, generic drugs are drying up.

On his blog, Centeno predicted that these shortages were due to “an ascendant hyper-regulatory FDA.” As it turns out, Centeno’s instincts were dead on. A Congressional hearing has confirmed that the FDA is responsible for the drug shortages. The “new FDA” focuses on reducing the so-called “type 1 regulatory” errors. Type 1 regulatory errors occur if a dangerous drug is allowed to go through market. It is certainly a proper function of the FDA to prevent type 1 regulatory errors. However, by overly focusing on type 1 regulatory errors, the agency is guilty of type 2 errors, in which good drugs are from the market.

The number of people harmed by type 2 errors is very large indeed. One estimate puts the number at 82,000 lives a year. Forbes Magazine documented the enormous rise in Warning Letters issued by the FDA. These Warning Letters have essentially shut down the production of generic drugs. These factories were shut down not because there was an actual problem, but because of theoretical risks due to current Good Manufacturing Practice violations.

The FDA employees that issued the letters did not take into account the consequences of their actions; namely that entire factories would have to shut down. A fair number of these manufacturers may or may not be able to reopen their production lines for these cheap medications because of the increased regulatory costs. Some of these companies may even have had to build new facilities. Many companies will simply drop the production line and this means less generic drugs. Also for many of these drugs, there are no brand name alternatives anymore, and the consequences of all this is that our hyper-regulatory FDA that has chosen to focus on reducing one type of regulatory error and by being only focused in one direction, they place the public’s health at risk.

What is the solution? We need a FDA that is as concerned with type 1 errors as they are with type 2 errors. This will balance these concerns so that the public is as protected from bad drugs as much as it’s protected from delays in promising therapies or shortages of generic drugs.

Reprogrammed Amniotic Fluid Stem Cells Provide Alternatives to Embryonic Stem Cells

According to a study published in the journal Molecular Therapy has shown that stem cell found in amniotic fluid can be differentiated into a state that is similar to that of embryonic stem cells. Researchers from Imperial College London and the UCL Institute of Child Health were able to reprogram amniotic fluid cells without having to introduce any extra genes. These findings mean that stem cells derived from donated amniotic fluid could be stored in banks and potentially used for therapies and in research. This would provide a viable alternative to the limited embryonic stem cells that are currently available.

In the womb, the fetus is surrounded and nourished by amniotic fluid. Amniotic fluid can be extracted by using a small needle and a process called amniocentesis, which is sometimes used to test for genetic diseases, routinely uses such a needle to remove amniotic fluid for genetic testing. Amniotic fluid contains stem cells that come from the fetus, and these cells have the ability to develop into different cell types, like stem cells in the embryo.

Imperial College and UCL researchers used stem cells from amniotic fluid that had been donated by mothers who underwent amniocentesis during the first trimester of pregnancy. The cells were grown on a gelatinous protein mixture in the lab and reprogrammed into a more primitive state by treating them with a drug called valproic acid. An extensive set of tests found that these reprogrammed cells have characteristics that are very similar to embryonic stem cells (ESCs). ESCs are capable of developing into any cell type in the body – a property known as pluripotency.

Even after growing in culture for some time, the reprogrammed cells were able to develop into of many different types, including liver, bone and nerve cells. Furthermore, these cells were also functional. The reprogrammed amniotic stem cells also maintained their pluripotency even after being frozen and rethawed.

The results suggest that stem cells derived from amniotic fluid could be used in treatments for a wide range of diseases. Donated cells could be stored in banks and used in treatments, as well as in disease research and drug screening. A previous study estimated that cells from 150 donors would provide a match for 38% of the population.

The ethical concerns surrounding ESCs has prompted many scientists to seek alternatives them. Other scientists are also interested in alternatives to ESCs since the availability of donor embryos is poor. Other research has shown that adult cells can become pluripotent if particular genes are introduced into them (so-called induce pluripotent stem cells or iPSCs). The production of iPSCs, however, requires the introduction of extra genes into the cells, often by using viruses. Such a technique, however, does not efficiently reprogram cells and there is a risk of introducing tumor-causing mutations into the cells. This new study is the first to induce pluripotency in human cells without using foreign genetic material. Pluripotent cells derived from amniotic fluid stem cells showed some traits associated with embryonic stem cells that have not been found in induced pluripotent stem cells from other sources.

Unfortunately, amniocentesis is associated with a small risk of miscarriage (~ one in 100).

Dr Pascale Guillot, from the Department of Surgery and Cancer at Imperial, said: “Amniotic fluid stem cells are intermediate between embryonic stem cells and adult stem cells. They have some potential to develop into different cell types but they are not pluripotent. We’ve shown that they can revert to being pluripotent just by adding a chemical reagent that modifies the configuration of the DNA so that genes that are expressed in the embryo get switched back on.

“These cells have a wide range of potential applications in treatments and in research. We are particularly interested in exploring their use in genetic diseases diagnosed early in life or other diseases such as cerebral palsy.”

Dr Paolo De Coppi, from the UCL Institute of Child Health, who jointly led the study with Dr Guillot, said: “This study confirms that amniotic fluid is a good source of stem cells. The advantages of generating pluripotent cells without any genetic manipulation make them more likely to be used for therapy.

“At GOSH we have focused on building organs and tissues for the repair of congenital malformations, which are usually diagnosed during pregnancy. Finding the way of generating pluripotent cells from the fluid that surround the fetus in the womb move us one step further in the this direction”.

Dr Caroline Johnston, Research Evaluation Manager with children’s charity Action Medical Research said: “These new findings could be a step forward for treatments of a wide range of diseases that affect babies and children. We are proud of our history of funding medical breakthroughs and of our support for these researchers in their move towards life changing therapies.