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A List of Possible FDA Reforms – Compilation by Dan Elton

A List of Possible FDA Reforms – Compilation by Dan Elton

Daniel C. Elton, Ph.D.


I have ranked these according to my own perception of which have the most support among DC bureaucrats and members of congress.

  • Improving transparency. During the COVID-19 pandemic the public has been kept in the dark regarding how key decisions were made, such as the decision to issue an EUA for hydroxychloroquine, the decisions that pushed Pfizer’s EUA from early November to late December, and the decision to require additional Phase III data from AstraZeneca which delayed their EUA by at least 3-4 months. Currently the FDA keeps much of the information relevant to decision making confidential. In theory Freedom of Information Act (FOIA) requests can be used to obtain some information, but in practice FOIAs are slow-walked, may require litigation, and take years to resolve. There are many possible ways to increase transparency at the FDA, some of which are outlined in this recent article in STAT News. 18 specific recommendations can be found in this journal article from 2018. One of people referenced as a top candidate for FDA Commissioner, Joshua M. Sharfstein, is a poor choice when it comes to implementing other reforms but has been a leading voice calling for more transparency.
  • Reciprocity. If a drug/medication is approved by a regulatory agency in a different country which has equivalent standards to the FDA (for instance agencies in the UK or Japan, the European Medicines Agency (EMA), or Health Canada), it should automatically be approved by the FDA (and vice versa). Reciprocity would save both taxpayers and companies a lot of time and money. Imagine if the AstraZeneca vaccine had been approved on January 1st, a few days after the UK approved it. It’s easy to see that tens of thousands of lives would have been saved, especially when you consider it would have been given to the most at-risk first!  In 2015 Senators Mike Lee and Ted Cruz introduced the RESULT Act, which is primarily focused on implementing reciprocity.
  • Making the agency independent from the executive branch. It’s hard to insulate the FDA from political concerns as long as Congress controls the FDA’s purse, but it could at least be removed from direct interference from the executive branch by making it an independent agency like the FCC or Federal Reserve. There seems to be wide support behind this idea right now and recently four former FDA commissioners all endorsed this idea in an interview.
  • Rolling reviews. It should not take 3-4 weeks from the submission of an EUA application until a decision is made, especially when thousands are dying every day while waiting for vaccines. According to Dr. Marty Makary, a professor of public health policy at the Johns Hopkins Bloomberg School of Public Health who has conducted over a hundred clinical studies, the FDA “could have done the approval in 24-48 hours without cutting any corners”. Likewise, the approval of drugs and therapies after Phase III trials have reached an endpoint should not take 6 – 18 months. While the FDA does engage in a back and forth with companies prior to when they submit their paperwork for an EUA or approval, they do not use rolling reviews. Due to their rolling review systems other countries like the UK were able issue EUAs for COVID-19 vaccines faster than the FDA. Rolling reviews should be the norm, and the submission and analysis of trial data should made as streamlined and as efficient as possible without compromising the integrity of the analysis.
  • Tiered approvals. Doctors who want to provide new drugs to at-risk patients currently have to wait 5-10 years for lengthy Phase III trials to conclude and then another 6 – 18 months for the FDA to carry out their review of the trial data. Tiered approvals would allow a lower level of approval after just Phases I and II, freeing up treatments to those who need them most. The centrist Niskanen center has a white paper which suggests four levels of approval (see also their op-ed in The Hill).
  • Expansion of Right-to-Try. Federal right-to-try legislation was passed in 2018. However, it is very restrictive, and patients need to have met a number of strict requirements before they can try new medications and treatments, greatly limiting its utility.
  • Treating aging as a disease. Currently it is illegal to market an FDA-approved product as a treatment for aging. Even though aging is a harmful biological process, it is not considered a legitimate “indication” for a drug or therapy by the FDA. In other words, the FDA doesn’t view aging as a “disease” and therefore anti-aging treatments fall outside their mandate. Some specific aspects of aging are also not considered as legitimate indications. The FDA is currently operating in an inconsistent way as some conditions which are due to the aging process can are considered legitimate targets, such as osteoporosis and menopause, but others, like sarcopenia (age-related muscle loss /frailty), are not.  Many experts, including David Sinclair, have spoken out about this issue. Some companies have found ways to get around the FDA’s restrictions, such as by using certain metabolic markers to track the degree of damage from aging. However, the impossibility of getting FDA approval for therapies that directly slow down or repair the damages from aging greatly dis-incentivizes industry R&D investment in this area.  Fortunately, with advanced gene and stem-cell therapies on the horizon, the Congress and the FDA have already taken a few steps towards being able to review and approve anti-aging drugs and therapies. The 21st-Century CURES Act, for instance, mandated the creation of the Regenerative Medicine Advanced Therapy designation at the FDA.
  • Challenge trials in emergency situations. Many people, including a group of legislators, lobbied the FDA to give companies the go-ahead to do challenge trials, but there was no action. Thousands of volunteers for COVID-19 challenge trials signed up with 1daysooner.org but were unable to participate as they had wished to. As a result, data on vaccine efficacy was obtained much slower than it could have been.
  • Use of the proactionary principle for all drug & therapy approvals. The FDA should publish a transparent, quantitative, scientifically informed, and structured cost-benefit analysis for each regulatory action performed, which estimates the expected quality-adjusted life years (QALYs) saved versus risk of QALYs lost for both the action and inaction. The analysis should be made public, ideally sometime before the decision goes into effect. Crucially, the analysis should enumerate the risks and benefits of granting an approval and the risks and benefits of not granting it. See Max More’s overview of the proactionary principle and his chapter in The Transhumanist Reader, where he presents not just a principle but an entire framework for rational decision making. The key reform here is to make it mandatory that decision making at the FDA be highly structured and quantitative so it under less sway from political concerns and cognitive biases. If such a framework for rational decision making was in place it’s unlikely the FDA would have decided to delay Pfizer’s Emergency Use Authorization (EUA) from early November to December 11th, a decision which cost tens of thousands of American lives.
  • Free to Choose Medicine with a Trade-off Evaluation Database.  In brief, Free to Choose Medicine would create an additional track after Phases I and II to allow doctors to prescribe new therapies to at-risk patients who are unable or unwilling to participate in a Phase III trial. Patients in the Free-to-Choose Track would be mandated to submit data to a trade-off evaluation database, creating a trove of valuable real-world data (this could be genetic, biomarker, and adverse events data, for instance).  See this excellent podcast interview with Bart Madden for more information. 

Figure from Bart Madden, “Free to Choose Medicine“, The Heartland Institute

 

Dan Elton, Ph. D., is Director of Scholarship for the U.S. Transhumanist Party.  You can find him on Twitter at @moreisdifferent, where he accepts direct messages. If you like his content, check out his website and subscribe to his newsletter on Substack. 

New FDA Regenerative Medicine Framework is Win-Win for Gene Therapies – Article by Keith Comito and Elena Milova

New FDA Regenerative Medicine Framework is Win-Win for Gene Therapies – Article by Keith Comito and Elena Milova

Elena Milova
Keith Comito


Editor’s Note: In this article, Keith Comito and Elena Milova positively discuss new a FDA regulatory framework on RMAT (regenerative medicine advanced therapies) and on how it benefits the healthy-life-extension community. This article was originally published by the Life Extension Advocacy Foundation (LEAF).

                   ~ Kenneth Alum, Director of  Publication, U.S. Transhumanist Party, March 3, 2018

Back in November 2017, the FDA announced a comprehensive policy framework for the development and oversight of regenerative medicine products, including novel cellular therapies. Both draft guidance documents had 90-day comment periods, and we at LEAF joined forces with the Niskanen Center to submit comments to the FDA to ensure that the voice of the community for healthy life extension was heard. These new regulations could have considerable implications for the therapies and technologies being developed as part of the biomedical gerontology field.

The first draft guidance addresses how the FDA intends to optimize its regulatory requirements for devices used in the recovery, isolation, and delivery of RMATs (regenerative medicine advanced therapies), including combination products.

The second document explains what expedited programs may be available to sponsors of regenerative medicine therapies and describes what therapies may be eligible for RMAT designation.

According to new FDA regulations, a drug is eligible for designation as an RMAT if:

  • The drug is a regenerative medicine therapy, which is defined as a cell therapy, therapeutic tissue engineering product, human cell and tissue product, or any combination product using such therapies or products, except for those regulated solely under Section 361 of the Public Health Service Act and part 1271 of Title 21, Code of Federal Regulations;
  • The drug is intended to treat, modify, reverse, or cure a serious or life-threatening disease or condition; and
  • Preliminary clinical evidence indicates that the drug has the potential to address unmet medical needs for such disease or condition

We hope that this joint project will support the improvement of US regulations that concern these innovative treatments and will make the overall regulatory landscape more friendly. Below, we cite the most important notes from our resulting paper.

Last week, the Niskanen Center joined with the Life Extension Advocacy Foundation in filing comments to the Food and Drug Administration (FDA), offering our support for the agency’s new regenerative medicine advanced therapy (RMAT) designation draft guidance for industry.

Although there are opportunities for marginal improvements to the guidance, and FDA approval processes more generally, we are happy to see that the agency chose to include gene therapies in its interpretation of what qualifies as a regenerative medicine therapy.

Under section 3033 of the 21st Century Cures Act, the FDA was tasked with developing an accelerated approval process for regenerative advanced therapies. Such therapies would qualify for expedited review and approval so long as the drug (a) met the definition of a regenerative medicine therapy, (b) was “intended to treat, modify, reverse, or cure a serious condition,” and (c) “has the potential to address unmet medical needs” for a serious disease or condition. Unfortunately, the bill’s definition of a regenerative medicine advanced therapy was unclear on whether gene therapies, in particular, would qualify. Luckily, the FDA clarified this point. As the RMAT guidance document notes:

gene therapies, including genetically modified cells, that lead to a durable modification of cells or tissues may meet the definition of a regenerative medicine therapy. Additionally, a combination product (biologic-device, biologic-drug, or biologic-device-drug) can be eligible for RMAT designation when the biological product component provides the greatest contribution to the overall intended therapeutic effects of the combination product.

This is an excellent development and one that portends immense benefits for future gene therapy applications submitted for FDA approval. According to the guidance, the new RMAT designation, unlike other fast-track approval and review processes, “does not require evidence to indicate that the drug may offer a substantial improvement over available therapies.” Liberalizing the threshold standards of evidence for RMAT designation ensures that future gene therapies will encounter fewer unnecessary roadblocks in delivering more effective and innovative treatments for individuals suffering from debilitating diseases.

As we note in our concluding remarks:

Overall, we consider the RMAT guidance to be a stellar improvement over other expedited programs, especially in its qualifying criteria. However, greater clarity is needed in order to capture the benefits of more advanced cell therapies that can help contribute to the healthy aging and well-being of American citizens. As FDA Commissioner Scott Gottlieb recently noted: “The benefits of [gene therapy] science—and the products that become available—are likely to accelerate. How we define the modern framework for safely advancing these opportunities will determine whether we’re able to fully realize the benefits that these new technologies can offer.”

We agree wholeheartedly. Developing a regulatory framework that accommodates safety and innovation will be a key determinant of how quickly the benefits of regenerative medicine, gene therapy, and anti-aging research revolutionize the lives of Americans. This guidance is an important and promising step in the right direction. With the right modifications, it can help usher in a new age of healthcare improvement for individuals from all walks of life.

Read the full comments submitted to the FDA here.

Source: Niskanen Center

About Elena Milova

As a devoted advocate of rejuvenation technologies since 2013, Elena is providing the community with a systemic vision how aging is affecting our society. Her research interests include global and local policies on aging, demographic changes, public perception of the application of rejuvenation technologies to prevent age-related diseases and extend life, and related public concerns. Elena is a co-author of the book “Aging prevention for all” (in Russian, 2015) and the organizer of multiple educational events helping the general public adopt the idea of eventually bringing aging under medical control.

About Keith Comito

Keith Comito is President of LEAF / Lifespan.io and a long-time advocate of longevity research. He is also a computer programmer, mathematician, musician, lover of life and perhaps a man with too many hobbies. He earned a B.S. in Mathematics, B.S. in Computer science, and M.S. in Applied Mathematics at Hofstra University, where his work included analysis of the LMNA protein.

About LIFE EXTENSION ADVOCACY FOUNDATION (LEAF)

In 2014, the Life Extension Advocacy Foundation was established as a 501(c)(3) non-profit organization dedicated to promoting increased healthy human lifespan through fiscally sponsoring longevity research projects and raising awareness regarding the societal benefits of life extension. In 2015 they launched Lifespan.io, the first nonprofit crowdfunding platform focused on the biomedical research of aging.

They believe that this will enable the general public to influence the pace of research directly. To date they have successfully supported four research projects aimed at investigating different processes of aging and developing therapies to treat age-related diseases.

The LEAF team organizes educational events, takes part in different public and scientific conferences, and actively engages with the public on social media in order to help disseminate this crucial information. They initiate public dialogue aimed at regulatory improvement in the fields related to rejuvenation biotechnology.