Why is a cell therapy that restores sight to the blind against the law?

FDA

A lot of people are frustrated with the US Food and Drug Administration (FDA) and its woefully slow process for approving stem cell therapies. That’s one of the reasons why we started the CIRM Stem Cell Champions campaign, to gather as many like-minded supporters of stem cell research as possible and help to change the way the FDA works, to create a more efficient approval process.

You can read more about that campaign and watch a short video on what being a Stem Cell Champion involves (hint: not very much).

Now Randy Mills, our President and CEO, has teamed up with former US Senator Bill Frist to explain precisely why the FDA needs to change the way it regulates stem cells, and to offer a simple way to create the system that will best serve the needs of patients.

This Op Ed appeared on Fox News’ online Opinion section on Friday, May 20th.


Cell therapy reversed blindness for 47,000 patients in 2015. So why is it against the law?

By C. Randal Mills Ph.D., Sen. Bill Frist M.D.

As medical miracles go, restoring sight to the blind is right up there. A mother seeing her baby for the first time, or a child being able to count the stars is a beautiful gift, and its value cannot be overstated. Last year 47,000 Americans received that gift and had their blindness reversed through the transplantation of cells from a corneal donor’s final selfless act.

It is safe, it is effective, and because it is curative, it is a relatively cost effective procedure. It is medicine at its most beautiful. And according to FDA regulations, the distribution of this cell therapy is in violation of federal law.

That’s right. The regulation says that no matter how competent the surgeon, the FDA must first approve cells from donated corneas as if they were a drug—a process that takes over a decade and can costs billions of dollars — all for a practice that has been successfully restoring sight for more than 50 years. And this is only one example.

The good news: the FDA doesn’t always adhere to its regulations and has not in this case.

The bad news: inconsistent enforcement creates uncertainty, deterring innovation for other unmet medical needs such as arthritis, back pain, and diabetic ulcers.

How did a country known for pioneering medical breakthroughs get here?

Appropriate regulation of living cells that treat disease is inherently complex. Some therapies, like corneal cell transplants, are well-understood. Others are far more sophisticated and can involve forcing cells to change from one type to another, cutting out defective genes, and growing cells in culture to expand their numbers into the billions. Although this may sound like science fiction, it’s the type of very real science that will revolutionize the practice of medicine. And it is a challenging spectrum to regulate.

Unfortunately, what we have today amounts to a regulatory light switch for cell therapy; one that is either OFF or ON. For some cell therapies there is essentially no pre-market regulation. But at some point of added complexity, often arbitrarily decided by the FDA, the switch flips to ON and the cell becomes a drug in the minds of the Agency. And the consequences could not be more profound.

A product can be introduced through the OFF pathway in days with no FDA review and at very little cost. The ON pathway on the other hand, takes 10-20 years and can cost over a billion dollars. For cell therapy, there is no in between.

It is not possible to regulate the continuum of cell therapies fairly and effectively by using this binary approach. The system is broken and is impeding the hunt for safe and effective treatments for suffering patients.

Why? Because sensible people don’t invest significant capital gambling that the FDA will give them a pass out of its rules. They evaluate the time and cost of development assuming they will be forced down the ON pathway. They also assume that this arbitrary approach to regulation will (and often does) work against them by allowing a competitor to enter the market through the OFF pathway, placing them at a prohibitive disadvantage. The results speak for themselves. After 15 years under this paradigm we have had only a few cell therapies approved, all commercial disasters.

This is because the ON-OFF approach fails to adequately account for the difference in cell therapy complexity. To better understand, imagine this methodology applied to the regulation of automobiles. The government might permit low tech cars, say the Model T, to be sold without pre-market regulation. But if a manufacturer wanted to improve the vehicle by adding air conditioning, a radio or other such feature, the car would be subject to massive pre-market regulation. And not just on the new feature. Instead, the addition of the new feature would trigger a bumper-to-bumper evaluation of the entire car, increasing its development cost from basically nothing to that of a Lamborghini. The result would be streets full of hot, radio-less go-karts, except for a few ultra-high-end sports cars whose manufacturers are now defunct because they were never able to recoup the disproportionate costs of satisfying the regulatory system. This is what we see with cell therapies today: progress that is sluggish at best.

How can we move forward?

Ironically, the FDA identified a solution to the problem. In order to account for the broad spectrum inherent to cell therapy, in the late 90’s the FDA proposed a progressive, risk-based approach. The higher the risk, the greater the regulation. This guards against under regulation that might put patients at risk and prevents overregulation that can disincentivize the development of new or improved products.

In the FDA’s own words, the regulation they proposed would abide by a few basic principles:

  • “Under this tiered, risk-based approach, we propose to exert only the type of government regulation necessary to protect the public health.”
  • “The regulation of different types of human cells… will be commensurate with the public health risks…”
  • “These planned improvements will increase the safety of human cells… while encouraging the development of new products.”

It was a remarkably common sense approach that would have balanced safety with the need for innovation over an exceptionally broad range of technological complexity and risk.

It would have.

Unfortunately, the regulatory framework that was promised was never delivered, and it is time to resuscitate it. The burden placed on the development of cell therapies must accurately reflect the risks; must be balanced against the very real consequences of doing nothing (patients continuing to suffer); and must be consistently and fairly applied. In short, the FDA had it right and we need to give them the tools to deliver the regulatory paradigm they originally envisioned.

If we fix this highly fixable problem, we can create a system that will drive new innovations and better outcomes. Europe and Japan have already acted and are seeing the benefits. People with great ideas are coming off the bench, and game changing therapies are entering practice. While challenging the status quo does not sit well with some, particularly those who stand to prosper from the built-in barriers to entry the current structure provides, in the United States we have a responsibility to do better for patients and fix this broken system.

Randal Mills, Ph.D., is the President and CEO of the California Institute for Regenerative Medicine

William “Bill” H. Frist, M.D. is a nationally-acclaimed heart and lung transplant surgeon, former U.S. Senate Majority Leader, and chairman of the Executive Board of the health service private equity firm Cressey & Company.

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5 thoughts on “Why is a cell therapy that restores sight to the blind against the law?

  1. In many instances the FDA HOLDS TENACIOUSLY TO IDEOLOGIES that have gone on beyond their validity in time and place. Positive responses to this negativism could elicit actions from congress that bring to light for all citizens the dilemma doctors face today.

  2. I recommend two upcoming FDA public meetings on stem cell therapy regulations, Sept 8 and Sept 12-13, 2016. Here’s a link: https://www.federalregister.gov/articles/2016/04/22/2016-09372/draft-guidances-relating-to-the-regulation-of-human-cells-tissues-and-cellular-and-tissue-based

    The meeting on the 8th is for “science”, and the one of the 12th is for regulations. They invite public comment, so please, if you can’t attend, give them some input.

    The last FDA meeting I attended was for Huntington’s and Parkinson’s disease patients, and it was very helpful in understanding the tensions between the FDA and patient advocates. I was very impressed that the patients were so well educated about the current scientific research.

    • Thank you for mentioning the FDA patient-focused meeting held last September for Huntington’s and Parkinson’s disease. I was there as a 73-year old Huntington’s patient WITHOUT Chorea. As you may know, there are only two FDA-approved drugs for Huntington’s, but strictly for chorea. I truly felt that the entire FDA panel of experts finally started to “get” why we are so upset without any drugs or treatment. It seems they were promising me to re-evaluate their whole approval process, and attempt to get clinical drug trials starting sooner without so much delay. I was impressed with their demeanor and attitude, and I think they had never seen a Huntington’s patient without chorea.

      However, we’re back to square one, we still have no drugs, treatments or cures for this disease. Prana Biotech. in Australia had one clinical drug trial for a drug called PBT2, and I was able to take part in the Phase-2 double-blind study. We took drug for 6 months, and continually watched for side-effects, and for possible abatement of some symptoms. I got better, my balance and mood improved, and there were no side-effects for me. We were waiting for the FDA to give their approval for Phase-3 drug trials to begin, and were so discouraged when they opted instead to give PBT2 “Orphan Drug Status”, forcing the drug manufacturer to apply for European Phase-3 approval. They recently completed that trial, with very promising results, and may have found a way to help the neurons improve. Prana expects to make an announcement at the Annual Global Movement Disorders Conference, being held fairly soon. My question is: what can we do right now to make sure the FDA approves this one drug that is safe, works for non-chorea symptoms, and seems to have residual long-term effects?

      • Dear Julie, thanks for that thoughtful reply. I can appreciate how frustrating it must be to know that there are therapies out there that look promising and may be able to help people with Huntington’s but that are not available. All I can do is encourage you to write to the FDA. As you know CIRM has recently launched our Stem Cells Champions campaign to try and get the FDA to make changes to the way it regulates stem cells, so that it has a more efficient, but no less safe, approval process. Our goal is to help move the most promising therapies into clinical trials to see if they do really work and can help people. We will keep working as hard as we can for as long as is necessary to make that happen.

  3. I AM AN 82 YR OLD PARKINSONS PATIENT. I HAVE PAID FOR MY OWN RESEARCH THRU KANSAS REGENERATIVE MEDICINE. I BELIEVE I HAVE BENEFITED GREATLY BY MY STEM CELL TREATMENT THRU THEM. A MAJOR FRUSTRATION THAT I HAVE IS SEEING VET MEDICINE PERFORM THE STEM CELL TREATMENTS , IDENTICAL TECHNOLOGY TO THAT FOR HUMANS, AT A MUCH LOWER PRICE .FOR DOGS. IT SEEMS TO ME, HUMANS OUGHT TO HAVE AT LEAST AS MUCH RIGHT TO GET STEM CELL TREATMENTS AS DOGS DO AT A SIMILAR PRICE.

    I THINK THE WHOLE STEM CELL THING SHOULD BE DE-REGULATED AND LET THE CHIPS FALL WHERE THEY MAY. SEEMS TO WORK OK FOR DOGS, US HUMANS JUST DONT GET IT.

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