The Blistering Pace of Genetic Medicine
In his book Permissionless Innovation, my colleague Adam Thierer documents the demand cycle that most emerging technologies usually follow: initial resistance, gradual adoption, and then complete assimilation of the technology into our daily lives. This cycle has been true for innovations ranging from cars to smartphones, and even controversial bio-technologies like in vitro fertilization.
Each new technology seems to move through the cycle more quickly than its predecessor. This chart below, created by Nicholas Felton of the New York Times and cited in a short piece by Columbia Business School professor Rita Gunther McGrath, shows just how much faster new products are reaching households.
McGrath points out that “It took decades for the telephone to reach 50% of households, beginning before 1900. It took five years or less for cellphones to accomplish the same penetration in 1990.” This is an absolutely astonishing change in the rate of adoption.
Arguably, the adoption rate of gene editing technologies like CRISPR, the bacterial immune system that was detailed in Dr. Jennifer Doudna’s 2012 paper, by the scientific and medical communities could beat even that of cell phones. A simple search for “CRISPR” on PubMed shows that in 2012, only 127 papers related to CRISPR were published. Only three years later in 2015, that number balloons almost ten-fold to 1,262 papers. The science is moving at a blistering pace.
First In Vivo Gene Editing in Humans
Last week, doctors reiterated this quick development by performing the first gene editing treatment in a patient’s body. Prior gene editing treatments were administered by extracting a patient’s cells, editing them in the lab, and then injecting those cells back into the patient’s body.
Doctors in California used a gene editing technique called zinc finger nucleases (ZFN) to treat Brian Madeux, who suffered from Hunter syndrome. Madeux’s body does not produce an enzyme needed to break down certain carbohydrates. These molecules build up and cause extensive damage that affects appearance, organ function, and physical abilities. Madeux has already undergone twenty six surgeries for Hunter syndrome-related conditions and has nearly died from the genetic disease.
Doctors used an IV to inject Madeux with the ZFN machinery that will locate and cut the defective gene from the DNA and a copy of the correct DNA sequence. If the gene editing works properly, the cell will use the properly functioning template provided by the doctors as it repairs the break in the DNA.
Madeux and his physicians will have to wait for at least a month for signs of the treatment’s effectiveness. After three months, tests can be performed to definitively confirm whether the gene editing worked properly.
FDA Pursues Nimble Approach
This incessant march from science fiction to reality has left regulators struggling to adequately respond to gene editing. The often lengthy lag between the development of new technologies like gene editing and the passage of regulations to govern those new technologies is what philosopher Wendell Wallach and other scholars have called the “pacing problem.”
However, despite the challenge of keeping up with gene editing science, the FDA, the main regulator in the field, announced several encouraging policy updates in an effort to provide more clarity on the regulation of regenerative medicine.
Commissioner Scott Gottlieb noted that regenerative medicine has seen “rapid growth” recently and that this has posed “unique challenges” to the FDA. The main challenge that he identified was striking the proper balance between encouraging further innovation of genetic treatments with extensive potential benefits, and ensuring these new treatments are safe and effective. This requires a framework that allows FDA to be “nimble and creative” when responding to genetic technology.
This goal of being more nimble and responsive seems to be the new obsession of the FDA. Thierer and I recently wrote about how the agency is aggressively pursuing this approach on digital health technologies in an essay called “‘Build & Freeze’ Regulation Versus Iterative Innovation.” FDA has long been a leader in innovative governance models, using mechanisms like guidance documents, public workshops, and best practices with increasing frequency.
Thus far, this “nimble” approach seems to be positive, fostering greater innovation in the life sciences sector. But it is easy to picture that more flexibility could just as easily be used to stifle technological development in the future.
Regenerative Medicine Policy Framework
The “comprehensive regenerative medicine policy framework” was announced through a suite of four guidance documents — two final documents and two draft documents.
According the press release:
The two final guidance documents clarify the FDA’s interpretation of the risk-based criteria manufacturers use to determine whether a product is subject to the FDA’s premarket review.
The first draft guidance explained FDA’s regulatory approach to devices used in connection with “regenerative medicine advanced therapies” (RMATs). This RMAT designation was established by the 21st Century Cures Act (codified in 21 U.S.C. 356(g)) as an expedited review program for “cell therapy, therapeutic tissue engineering products, human cell and tissue products, and combination products using any such therapies or products.”
The guidance reasserted FDA’s three tiered system of device classifications based on a device’s risk level. How a device is classified then determines what kind of premarket regulation is applied to the device. The agency then briefly explained the proper application procedure for each pathway. The document also reassured device manufacturers that the agency is committed to only requesting the minimum amount of data needed to support a device’s approval. Finally, “The guidance specifies that devices intended for use with a specific RMAT may, together with the RMAT, be considered to comprise a combination product” and can be reviewed under a single application.
The second draft guidance detailed the expedited programs available to developers of regenerative medicine therapies. The five designations that the guidance explained were Fast Track, Breakthrough Therapy, RMAT, Priority Review, and Accelerated Approval.
The new RMAT designation is only applicable if a treatment falls under the statutory definition of an RMAT referenced above, in intended to treat a serious condition, and evidence suggests the therapy has the potential to address unmet medical needs for such a condition. Advantages of the RMAT designation include expedited FDA review, “intensive FDA guidance on efficient drug development,” and “organizational commitment to involve senior management in facilitating the product’s development program.”
Conclusion
The FDA’s recognition that the traditional, slow method of regulating no longer works when science moves at an increasingly astonishing pace is encouraging. The understanding of the beneficial potential of regenerative medicine and the commitment to fostering innovation in this sector bode well for the future of the life sciences. The policy framework provides researchers and biotech companies with the information and tools they need to speed their treatments through the regulatory process.
Still, I am concerned that the nimble agency apparatus that current FDA officials seek to develop could be abused in the future and end up stalling innovation and harming patients.
Additionally, I would like to see more research done on the interactions between FDA and industry, especially in light of recent programs like RMAT. How much do these designations involve agency officials in the treatment development life cycle? What are the consequences, both good and bad, of increased collaboration between agency and industry?
In the case of increased collaboration, one likely consequence that I could foresee is a reinforcing of FDA’s soft law powers. An intimate role in the actual development of treatments means more influence over industry players and less need for more transparent means of influence like guidance documents, enforcement actions, and public workshops.
Research into these questions could determine if further controls on these possible practices are needed.
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Additional Reading
“Build & Freeze” Regulation Versus Iterative Innovation
Will Genetic Editing Advance Faster Than Our Ability to Regulate It?
