Wall Street Journal Opines on FDA and Stem Cells

Scott Gottlieb (physician) and Coleen Klasmeier (attorney) have penned an excellent op-ed piece in the Wall Street Journal that tasks the FDA for their unbending regulatory caprice and unwillingness to adapt to the new advances in medicine. It is definitely in line with what Centeno has been saying for these long years. Read it here.

They are reasonable troubled by the DC court’s uncritical acceptance of the FDA’s arguments and note:

“The FDA has repeatedly sought to blur the line between manufacturing medical products and practicing medicine whenever new techniques emerge. But the standard for regulation isn’t whether the agency feels a technique is novel but whether it meets the definition of being a medical product.

Federal regulators have stretched that definition to the point where a reasonable limit no longer exists. The law provided a clear impediment to unrestrained exercise of FDA authority. Something needed to be an “article”—not a medical procedure—in order to become a drug. The constraint that a drug needed to be a “thing” has been read out of the law by FDA, and the district court appears to have accepted that position.

If the FDA’s victory is upheld on appeal, then conceivably nothing done as part of clinical practice is beyond the agency’s reach.”

They also sadly note:  “Most of the science of using adult stem cells for regenerative medicine is unfolding in Britain, Singapore and Israel precisely because of the FDA’s bent to hold with misgiving anything novel in medicine.”  Reform the FDA.  To do that we need a new president.

Centeno Responds: Part 2

In the last post, we saw that the FDA’s illegal fast-track approval of Genzyme’s cell-based Carticel product as a drug set a precedent that cells had to be treated as drugs and any cell-based therapy had to go through the extensive, expensive and invasive approvals for other types of pharmaceuticals.

This move put the kibosh on the development of cell-based therapies, since such therapies would have been massively expensive.

Centeno thinks that the FDA’s move stifled a potential renaissance in American medicine that would have been on par with the discovery of antibiotics. This might be a severe overstatement, but it seems clear to me, at least, that the FDA’s move did slow down the development of cell-based therapies.

Professional societies were no at all pleased with this regulatory move, since it would slow down the availability of therapies for patients. For example, te Society of Clinical Oncology, which represents 30,000 cancer specialists, sent a letter to the FDA on August 10, 1998 that read: “A striking aspect of the FDA’s proposal to regulate stem cell procedures is the virtual absence of any justification for the initiative. The principal “concerns” previously cited by the FDA in support of the new regulatory apparatus are preventing the transmission of communicable diseased and assuring that stem cell procedures are safe and effective.”

Certainly, these are valid concerns, but the letter continued: But, the FDA has adduced no evidence whatever to suggest that communicable diseases are presently being spread through stem cell procedures, or that stem cell transplants are unsafe or ineffective. Instead, the FDA has proposed to subject physicians and facilities performing stem cell procedures to an extraordinarily burdensome and restrictive regulatory regime based solely on theoretical issues.”

Wow! In other words, “your concerns are not real.” Furthermore, “you have no evidence to document your concerns and they only exist as possibilities.” In other words, according to these cancer specialists, the FDA created a policy to fix a problem that did not exist.

Certainly, the FDA could make the argument that the regulation guarantees that such problems will not pop up anytime soon, this misses the point of regulation – to address actual problems and not imaginary ones.

At this point Centeno makes a horrible historical blunder when he mentions the “Bush Administration’s ban on embryonic stem cell research.” For the umpteenth time, “THERE WAS NO BAN ON EMBRYONIC STEM CELL RESEARCH DURING THE BUSH ADMINISTRATION.” There I got that out. There was a moratorium on the use of federal funds for research that derived new embryonic stem cell lines, since such work required the destruction of human embryos. Private funding could fund such work, and embryonic stem cell research that used already established, approved ESC lines was eligible for federal funds. In the meantime, work on adult stem cells advanced during this time and some treatments became available.

Centeno thinks that drug companies supported by universities wanted to offer embryonic stem cells (ESCs) in vials, which would be administered and approved by the FDA in the way any drug would. Adult stem cells, on the other hand, came from the patient’s own body, and therefore, had a rough time fitting into this paradigm. The FDA, therefore, decided the alter the wording of a statute to include adult stem cells.

21 CFR 1271 regulations allowed any cells that came from a patient’s own body (autologous) to be regulated as a transplant or not at all. Therefore, any competitor of Genzyme could simply use their adult stem cell procedures without going through the lengthy and extensive approval process. It also meant that physicians, who are not directly regulated by the FDA, could start their own stem cell procedures without any FDA oversight.

The FDA however, solved this problem by altering one word in the statute from “into another human” to “into a human.” This change was apparently made without the public comment period required by the law. Even though this change seems minor, it means that cells from your own body cannot be placed into you without the FDA’s approval. In this manner, the FDA inserted itself into the lives of doctors.

Mary Ann Chirba, J.D., D.Sc., M.P.H. at the Boston College Law School gave the FDA a screen-full when she used her keyboard to critique the FDA’s language change. She said of this regulatory change that “in revising §1271.3(d) without the benefit of public input, the FDA has fashioned a regulation that imposes real and extensive burdens on patients and providers while achieving little if any benefit — at least with regard to low-risk, autologous adult stem cell therapies.” Not everyone is taking this change lying down.

One point Chirba makes is quite telling. She notes that the FDA has no such regulatory strategy when it comes to in vitro fertilization (IVF) therapies for infertile couples. IVF involves the harvesting of oocytes (eggs) from the presumptive mother and sperm from the presumptive father, the use of these cells to achieve fertilization in the laboratory, culture of the embryos outside the body, and then reintroduction of the cultured embryo into the mother’s body. Note the similarities of this treatment with autologous stem cell treatments – retrieval of cells from the patient, culturing the cells to make something different, but related to the originally harvested cells, and then the transplantation of those cells into the patient. The similarities are uncanny except that the FDA regulates autologous stem cell treatments but not iVF. Confused? Maybe you should be, because I am too.

If the FDA regulated IVF, they would achieve little in the way of safety, but the cost of the procedure would explode (however, the embryos might be better protected, but the FDA seems little concerned with human embryos these days, but that’s for another post).

The contradictory nature of this regulatory change has generated some terrific contradictions. For example, the FDA does not regulate bone marrow transplants, and in some cases, umbilical cord blood is used for such therapies instead of bone marrow.  By 2009, there had been 15,000 cases of umbilical cord blood transplantation, and cord blood was saving lives and was relatively unregulated by the FDA.  Then in 2009, the FDA changed tack and decided that cord blood was a drug and required approval.  Cord blood “drugs” received approval in 2011, but nothing changed with regard to its safety profile and use.  First it’s not a drug then it is; what’s up?

Another example is fat tissue used by plastic surgeons.  Plastic surgeons have been using fat for transplantation for years without FDA approval, but now, according to the FDA, is the fat is broken down in any way before it is reintroduced, then it is a drug.  Your own fat is now a drug!  Ridiculous?  You bet it is!  Then there is Cytori Therapeutics who have designed and manufacture a machine that isolates fat-based stem cells from fat.  According to the FDA, this machine manufactures and drug and must be vetted like a drug.  The machine is approved in Europe, but not in the US because the FDA is too busy sending warning letters to Cytori telling them to cease and desist unless the almighty FDA tells them they can proceed.

There are also some genuine tragedies that come with this stunt pulled by the FDA.  For example, Allosource and Parcell Laboratories process cadaver bone for bone transplants.   However, because the bone contains stem cells, according to the FDA, they are making a drug and require the huge piles of money it takes to receive FDA approval.  Then there is Provenge, a revolutionary treatment for prostate cancer that takes white blood cells from your own body and then reprograms them in culture to attack the prostate cancer.  Thanks to the excessive regulation of the FDA, one dose of Provenge costs $93,000.  Then there is the very sad case of Reprogenesis, who made a stem cell-based treatment for children with Vesicoureteral Reflux or VUR.  Even though the treatment uses the patient’s own stem cells to build a new urinary valve in the ureter, the FDA said that they were making a drug and needed approval for it.  Reprogenesis went bankrupt thanks to the FDA and children with VUR do not have that therapy.

If this sounds nuts, that’s because it is.  Don’t get me wrong, we need the FDA and we need an agency to safeguard the safety and efficacy of the medicines we take, but the FDA is working on a model that is 3-4 decades out of date.  American medicine is missing the renaissance in science because of overregulation and unwise regulation.  It needs to change.


Centeno Responds to The DC Court Decision: Part 1

The DC court case that ruled that cells = drugs upheld an injunction placed upon Regenerative Sciences by the FDA to not provide their Regenexx-C treatment unless they sought official FDA approval. Dr. Centeno, one of the major shareholders in Regenerative Sciences and its chief spokesperson, who also developed many of the treatments used at the Colorado clinic, has responded to the court ruling and the FDA in an ebook entitled “The Stem Cells They Don’t Want You to Have.” In our next few posts, we will discuss his response.

According to Centeno, in this country, there are two layers of regulation for medical procedures, treatments, and devices. Federally, the FDA has device and drug laws that they enforce. Their laws dictate what drugs and devices are approved and the clinical uses of these drugs a devices. Secondly, each state has regulations that direct the practice of medicine within their borders.

The FDA regulates those drugs and devices that are used throughout the nations and across state lines. Physicians, however, are not regulated by the FDA. This is an important point, because the FDA does dictate how the physician practices medicine. The state regulates the practice of medicine within its boundaries, but the FDA regulates the drugs and devices used across state lines. These two layers are regulation are meant to provide checks and balances to the regulation of medicine.

The importance of these checks and balances is that the physician is meant to do whatever is necessary to save your life, improve your health, or reverse a particular illness. The FDA does not have to like it, but they do not traditionally have the authority to do anything about it.

The FDA, however, has tried in the past to buck this system. For example, there is a practice in clinical practice known as “off-label” usages of drugs. Such usages involve prescription of a drug for a malady for which the FDA did not provide approval. For example, proton, pump inhibitors, such as omeprazole, for acid reflux disease, have been prescribed off-label because some physicians have noticed that they can quell severe diarrhea. Why they would do this is unclear, but it is the observation that they do. Therefore they are prescribed for such purposes. The FDA is not always alright with that, and in 1978, in United States v. Evers, the FDA sued Dr. Ray Evers for his use of calcium disodium versenate, a drug normally used in metal poisoning, as a treatment for arteriosclerosis. The court found for Evers in this case even though the weight of expert opinion was against the efficacy this drug as a treatment of arteriosclerosis. The Evers case established the ability of physicians to prescribe drugs off-label. In the words of Centeno, the court “preserved as sacred the right of your doctor to prescribe any drug in any way to save your life.”

The FDA, however, is not happy with this arrangement, and has been seeking ways around it. In the 1990s, the FDA attempted to crack down on pharmacies and physicians that “compounded” drugs. If a patient has a medical need that is not met by the available formulations of medicines, then the physician may ask to pharmacy to modify the formulation or combine it some other component. For example, if a medicine is pelleted with a tablet that contains gluten but the patient does not tolerate gluten, then the doctor can ask the pharmacist to prepare a gluten-free version of the medicine. Alternatively, if the patient is an infant and extremely low doses are required for a particular drug, then the doctor may ask the pharmacist to cut the drug with something else to lessen the dosage, or produce very tiny dosages in the traditional form. The FDA attempted to add a section to the Food, Drug and Cosmetic Act to regulate compounding, but they were defeated after a consortium of compounding pharmacies sued the FDA.

In the 1990s, when cells were used to treat patients, the FDA tried a different tact, since it seemed unlikely that they could properly regulate cells. After all, cells are neither drugs nor medical devices. This came to a head in 1995 when Genzyme began to culture the cartilage cells from patients to make a product known as Carticel. Carticel consisted of a patient’s own cells that had been cultured outside the body. Then they would give the cultured cells to a surgeon for implantation into the knee. How could these be regulated as a drug?

The FDA was concerned because culturing cells could introduce animal viruses into them or some other contaminant that could harm people. Therefore, there had to be some way to regulate this product in order to safeguard the health of patients. As you can see, the FDA are not monsters. They do want to help patients, but they are simply overstepping their bounds, according to Centeno.

Back to Carticel. Initially one division of the FDA had granted Genzyme clearance to market Carticel as a medical device. However, another branch of the FDA called the Center for Biologics Evaluation and Research or CBER told Genzyme that they had to have full and clear FDA drug approval in order to market Carticel.

What could Genzyme do? Without FDA approval, they were stuck, but getting FDA approval would require years and millions of dollars. Why FDA required drug approval for something that was not a drug was a mystery, but Genzyme was in no mood for a brawl with the FDA. They had a promising technology, but without approval, they could not sell it, and if they did not sell it, another company would pick up the technology and make it work with the FDA.

Therefore, Genzyme made a deal with the FDA. CBER wanted to call the cell drugs, but they ran into lots of opposition from powerful opponents: The Red Cross, The American Society of Clinical Oncology, The Society for Reproductive Technologies, and the BioPharma Association. According to Centeno, a Genzyme lobbyist told the FDA that they had to regulate cells, otherwise, Genzyme would have no way to protect its investment. The FDA acquiesced with the proviso that it would fast-track Carticel if the FDA was able to regulate cells as drugs.

It was this “Midnight deal,” according to Centeno, that paved the way for the FDA to call cells drugs and regulate them accordingly. Carticel was approved in nine months when the regular time for drug approval was seven years. There was a problem with this fast-track approval: The 21 CFR 601 statute was meant for the approval of drugs for treating critically ill patients. Carticel did not meet this requirement, which makes the use of fast-tracking in this case illegal.

As a result of this deal, other drug companies that developed or were developing cell-based therapies simply fell in line behind Genzyme and went through the FDA process for drug approval of their non-drug-based therapies.  FDA drug approval became, in the words of Centeno, the “gold standard” for cell base-products.

An evaluation of this situation will be discussed in a later post.

Obamacare: The Aftermath

Since many have asked my what I think about Obamacare and the recent Supreme Court ruling, I thought that I might provide my views on the topic.

In the first place, the law is obviously unconstitutional. The federal government cannot compel you to buy something. There is simply no universe in which someone can read our Constitution and come to the conclusion that the Constitution gives the government that power over its citizens.

Secondly, if Obamacare is a tax, then the lawsuit before the Supreme Court would have been dismissed, because according to the Anti-Injunction Act Donald Verrilli argued before the Supreme Court that the individual mandate is NOT a tax. However, in order to find the bill constitutional, Roberts had to treat it as though it was a tax. But wait a minute. The Anti-Injunction Act says that you cannot contest a tax bill until the tax is paid. Therefore, if Obamacare was a tax, then the case should have been dismissed til the tax was collected. Thus for the sake constitutionality, Obamacare is a tax, but for the sake of litigating it, it is not a tax. Roberts tried to have it both ways, but he can’t. This is the reason why legal pundits all over the US are troubled by Robert’s garbled, self-contradictory opinion. If this was a principled ruling then why did it make no internal sense.

Third, Obamacare is unworkable. In the words of Holman Jenkins of the Wall Street Journal, Obamacare is “upheld and doomed.” The problems with Obamacare are four-fold and they are :

1. Taxes

Besides being a massive federal power grab, Obamacare contains one of the largest tax increases ever imposed on the American economy. These tax increases come at a time when job growth should be the nation’s number one priority.. The tax sections of Obamacare begins with an increase in the Medicare payroll tax of 0.9 percent for individuals with incomes above $200,000 ($250,000 for couples) in 2013. Needless to say, this tax will depress the demand for labor at a time when job creation is critical in order to for jump-start the economy. Some might think that this tax will not hit the middle class because of the relatively high initial income thresholds, but they are wrong. These income thresholds were purposely not indexed to inflation. Therefore, as the years pass, more and more middle-income families will cross the thresholds because of normal wage growth.

Obamacare also includes an additional 3.8 percent tax on investment income; a new 2.3 percent excise tax on medical devices that will reduce the size of the industry. It also includes taxes on the drug and insurance industry that will be passed on to consumers in the form of higher premiums; and a tax on high-premium insurance plans that will also be passed on to consumers.

2. Deficits and Debt

Obamacare will exacerbate our nation’s already alarming entitlement spending and debt crises. The dramatic rise in spending on Medicare and Medicaid already is pushing the federal budget to the breaking point. Obamacare makes the problem much worse since it adds two new additional entitlement programs in the form of a massive Medicaid expansion and a new premium credit entitlement for households with incomes between 138 percent and 400 percent of the federal poverty level. These two entitlement expansions are expected to add a minimum of 35 million Americans to the entitlement rolls when phased in, at an expense of more than $200 billion annually by the end of the decade (CBO, Letter to House Speaker Nancy Pelosi, March 20, 2010, Table 4.).

Obamacare was sold by means of offsetting cuts in Medicare that supposedly would pay for it. Unfortunately, the Medicare cuts have been exposed as unrealistic because they would result in Medicare paying even less for medical services than Medicaid does today. (John D. Shatto and M. Kent Clemens, “Projected Medicare Expenditures Under Illustrative Scenarios with Alternative Payment Updates to Medicare Providers,” Office of the Actuary, Centers for Medicare and Medicaid Services, May 18, 201). This would severely jeopardize seniors’ access to care. Even worse, the offsetting cuts were made, the savings are double-counted under Obamacare, and are used once to pay for future Medicare commitments that are today counted as unfunded governmental liabilities, and then a second time to supposedly cover the costs of Obamacare’s entitlement expansions (Charles Blahous, “The Fiscal Consequences of the Affordable Care Act,” The Mercatus Center of George Mason University, 2012). Since money cannot be used twice, Obamacare will add hundreds of billions of dollars in new debts this decade, and trillions over the longer term (James C. Capretta, “The Medicare Trustees’ Report and the $8.1 Trillion Double-Count,” The Weekly Standard Blog, April 24, 2012).

3. Individual Mandate

The individual mandate hands immense regulatory power to the Department of Health and Human Services (HHS). According to Obamacare, HHS controls just about every aspect of the nation’s health system. In January 2012, the Administration announced that it planned to use that power to impose new benefit requirements on all employer-sponsored insurance in the name of “preventive health services” (now frequently termed the “HHS mandate”).

Additionally, the regulations issued by the Administration in this regard would require all employers, including religious employers such as Catholic hospitals and universities, to cover abortifacient products, contraceptives, and sterilization procedures in the health plans they offer to workers. By requiring all employers to offer these products and services in their health insurance policies, they would directly violate the religious liberty rights of thousands of religious institutions around the country.

4. The Bureaucratic Micromanagement of American Health Care

The bulk of Obamacare is based on the theory that the federal government has the capacity and know-how to micromanage American health care. This is the basis for the provisions that establish an unaccountable and unelected board—the Independent Payment Advisory Board (IPAB)—to oversee all aspects of how Medicare is run. It is also the theory behind Accountable Care Organizations (ACOs), which are authorized in Obamacare to give the federal government a new role in influencing how doctors and hospitals are organized to deliver care to seniors.

Unfortunately and contrary to socialistic preconceptions, the government is NOT adept at micromanaging how health care or any other aspect of people’s lives. When the government is given this much authority and discretion, it does not result in higher-quality care for patients. Instead, it leads to price controls and one-size-fits-all regulations that misallocate resources and lead to access problems. Obamacare compounds the problem since it creates massive new and costly bureaucracies at the federal and state levels of government that will become permanent and unresponsive centers of power. The IRS and HHS will grow. A new agency in HHS is slated to spend $10 billion supposedly testing new ideas, but already there is indication that the money is being wasted on projects driven more by politics than substance.

Obamacare is also pours hundreds of millions of dollars into the states to coax them into building the “exchanges” that will become the foundation of the Obamacare edifice. These exchanges, far from fulfilling the supposed mission of fostering a dynamic marketplace, will be the means by which the federal government will extend its reach to every corner of the health sector. Every American who does not obtain his or her insurance through an employer will have little choice but to go through Obamacare’s exchanges.   It will only be a matter of time before the federal government uses its new powers to impose even more top-down cost controls on the health system, to the detriment of the quality of American health care.

Obamacare is a disaster. Had the Supreme Court ruled properly, we would be out of this mess, but as it sits now, repeal – complete and total repeal – is the only answer.