Good Guidance for Cell and Gene Therapies
Safety Assessment
Shawna Jackman, PhD

Good Guidance for Cell and Gene Therapies

The FDA’s actions address the promise of innovative products and mounting concerns over stem cell clinics

Last week, the Food and Drug Administration’s moved to accelerate the review of extremely complex gene therapies and cellular therapeutics, while vowing to crack down on so-called stem clinics peddling dubious products derived from a person’s own stem fat cells.

The quartet of guidance documents, two of them brand-new and two of them finalized after the draft review and questions period, will, according to the FDA, “provide a comprehensive policy framework for the development and oversight of regenerative medicine products, including novel cellular therapies.”

There is no doubt that these are significant moves by the FDA. The fields of cell and gene therapy, which have seen a share of clinical development setbacks over the years, and are on the upswing again, and we are even starting to see some products reach market, notably the two chimeric antigen receptor (CAR) T cell drugs that represent a new phase in the nascent field of cancer immunotherapy. The drugs work by engineering a person’s own immune cells to fight cancer. The two new draft documents issued by the FDA on Nov. 16 build upon the FDA’s existing risk-based regulatory approach to more clearly describe what products are regulated as drugs, devices, and/or biological products. They also adhere to the requirements of the 21st Century Cures Act passed by Congress last year, which was signed into law to help accelerate medical product development and bring new innovations and advances to patients who need them faster and more efficiently.

So what this means is that if you have developed a gene therapy that cures a currently untreatable genetic disorder or a cell therapy that achieves a remission rate of 70-90% for a rare type of leukemia—as was the case with the most recent CAR T drug approved by the FDA—the regulatory process should be much faster than it was before.

Because gene and stem cell therapies have the capacity to fill tremendous unmet medical needs, for diseases that are often fatal, it makes sense for regulatory authorities to expedite these applications. These rapid pathways include the new Regenerative Medicine Advanced Therapy Designation created under the 21st Century Cures Act, and older programs such as Priority Review, where the FDA can take action within six months rather than the nine months under standard review, and Accelerated Approval, which allowed drugs for serious conditions that fill an unmet medical need to be approved quickly.

The new FDA draft guidance documents also addresses how the agency intends to simplify and streamline its application of the regulatory requirements for devices used in the recovery, isolation, and delivery of regenerative medicine advanced therapies.

Problematic therapies

Also in last week’s announcement is the anticipated risk-based approach to enforcement approach of the FDA to stem cell clinics, which offer unapproved treatments for all kinds of debilitating and incurable diseases using a patient’s own fat stem cells. Many of the clinics are peddling dubious products that until now have been operating outside of the law. One of the final guidance documents from the FDA explicitly says that “we are informing manufacturers, healthcare providers, and other interested persons that over the next 36 months, we intend to exercise enforcement discretion under limited conditions with respect to the investigational new drug application and premarket approval requirements, for certain human cells, tissues, and cellular and tissue-based products.” A second final guidance document provides greater clarity around when cell and tissue-based products would be excepted from the established regulations if they are removed from and implanted into the same individual within the same surgical procedure and remain in their original minimally manipulated form.

This long-awaited move by the regulatory agency hopefully will address the hundreds of clinics, which I’ve blogged about here and here, where the source of the cells and types of handling are not always clearly defined, making the treatments a safety concern and allowing the manufacturers offering these product to operate outside of the regulatory review process.  

It is truly an energizing time for cell and gene therapies and the commitment from the FDA to keep these products safe while expediting them to the patients will realize the imminent promise of these therapies in the clinic possibly sooner than initially expected.