US FDA and Unproven Cellular Therapies

Why you should care about the End of the Discretionary Period and the issuing of Warning and Untitled Letters.

What is happening and why?

“After May 31, 2021, FDA no longer intends to exercise enforcement discretion with respect to the IND and the premarket approval requirements as described in its Compliance and Enforcement Policy Regarding Certain Regulatory Requirements.”

On 09 July 2021, The US FDA declared the end of the discretionary period with regards to unregistered and unproven stem cell clinics. The most recent post indicates that the US FDA will no longer look the other way when companies claim that their stem cells will cure everything. The US FDA is now investigating the companies that are marketing cellular therapies as a medical treatment, as the US FDA defines those treatments as a biological drug product. As a result, the FDA has sent out numerous warning or untitled letters to Clinics advertising Regenerative Medicine or Stem Cell Therapies. It’s been a long three years since the original announcement of the discretionary period and stem cell clinics have popped up like mushrooms.

Who is being impacted by this?

Companies selling services that are injections of stem cells into people’s eyes, brains or bodies as “regenerative medicine” or “practice of medicine” are generally the target of the original notice from 2018. These institutions don’t believe that they are subject to FDA registration as they contend that they are practicing medicine not manufacturing drugs.

If your institution is registered with the FDA, you can be fairly certain that it will not be a target of this policy. Academic institutions in particular tend to have a lot of oversight in terms of Clinical Research department, IRBs and DSMBs. Finally, if you have an IND for your cellular therapy product, you are not subject to this policy.

Why should you care about this?

News organizations have reported multiple instances in which people have gone blind (see SCOTS results reported in the NEJM) or contracted a communicable disease (there’s a great podcast called Bad Batch - I recommend it!). If you have a moment to read the US FDA warning letters, they are a rich source of “what not to do” in your facility. For example, my favorite citation is this one:

“Failure to establish and follow appropriate written procedures designed to prevent microbiological contamination of drug products purporting to be sterile, including procedures for validation of all aseptic and sterilization processes [21 CFR 211.113(b)]”

Which indicates that the facility isn’t trying to keep their cellular products sterile during the time that the cells are out of the body. In a lot of cases it’s clear that the facility lacks a basic Quality Program and is not monitoring either the products or the process. When you look at your own processes, remember that something is better than nothing and that you should strive to make improvements every day. If you need a little help, remember Chimera TQM is here for you.

Finally, if you have any friends or family members who are considering treatments at such companies, you can send them to the FDA website specifically for patients. There’s a good list of items to consider at the bottom of the page. ISCT and ASGCT also have patient resources about cellular therapies.

Definitions

US FDA United States Food and Drug Administration

IRB Internal Review Board

DSMB Data, Safety and Monitoring Board

IND Investigational New Drug

SCOTS Stem Cell Ophthalmology Treatment Study

NEJM New England Journal of Medicine

ISCT International Society for Cell and Gene Therapy

ASGCT American Society for Gene and Cell Therapy

References

FDA Website: Questions and Answers Regarding the End of the Compliance and Enforcement Policy for Certain Human Cells, Tissues, or Cellular or Tissue-based Products (HCT/Ps), retrieved 26 July 2022 https://www.fda.gov/vaccines-blood-biologics/cellular-gene-therapy-products/questions-and-answers-regarding-end-compliance-and-enforcement-policy-certain-human-cells-tissues-or