The New York Times just broke a story on Burst Biologics and Weill Cornell that fits with long-standing troubling questions about regenerative biologics producers. The story also bears on the doctors and hospitals like Weill Cornell that were or are customers of the suppliers. Further, what is the FDA’s role in all of this?
The piece is entitled: How Much Do Patients Need to Know About a Potentially Risky Treatment? (As a sidenote, I sometimes have dinged news outlets, even the New York Times for their over the top headlines, but this one seems to go the opposite direction. It says nearly nothing, which is odd.) The story is a lot more interesting than the headline in this case.
The NYT reporters detail how Burst Biologics sold what the FDA has characterized as an unapproved drug to some high-profile hospitals, including Weill Cornell.
Weill Cornell then used the umbilical cord product, called BioBurst, on patients.
It is unclear if any patients were harmed as a result. It appears Weill Cornell did not notify patients about what happened.
Was there even some kind of a cover-up at Weill Cornel?
Burst Biologics and the FDA
For background, the FDA previously warned Burst Biologics that some of its products were unapproved drugs. The FDA warning letter, to firm leader Christopher D. Jones, also detailed CGMP and CGTP problems. These manufacturing issues raise concerns about potential exposure of patients to pathogens.
The NYT article is subtitled:
“An unapproved product made from umbilical cord blood was used at a prominent New York hospital. After an F.D.A. warning came an internal complaint: Patients should have been told.”
When I read that subtitle I had a bad sense of deja vu about the perinatal biologics space, which I’ve been covering for years. There has been so much going wrong in that area and harm to customers/patients. The NYT piece begins:
“A visiting researcher at NewYork-Presbyterian/Weill Cornell Medical Center was startled when he read the warning from the Food and Drug Administration about a product that had been used in spine surgeries at the esteemed Manhattan hospital.”
How did Weill Cornell end up using an unapproved biological drug on patients?
Biologics suppliers and their doctor customers
Perinatal or birth-related regenerative material suppliers have been aggressively marketing their products to doctors and hospitals for about six years. These biologics are often unapproved drug products. However, the doctors and hospitals usually don’t know that.
This seems to be what happened at Weill Cornell at first.
The suppliers sometimes even tell the potential customers that they have or don’t need FDA approval. Or it’s implied.
By the time the FDA warned Burst Biologics, the company had already sold some of its products like BioBurst to many customers including Weill Cornell.
Was it used by some hospitals even beyond the date of the FDA warning to Burst? It’s hard to be sure about the timing in many cases.
Regenerative cover-up?
Here’s what the NYT says about Weill Cornell (the advisory being the FDA warning letter to Burst), which indicates the patients got the unapproved drug before the public FDA warning letter about it:
“Yet before that advisory, about 40 patients at the hospital had received treatment with the fluid under the direction of Dr. Roger Härtl, a senior surgeon and professor at Weill Cornell, who is also a physician for the New York Giants. The surgeries were documented in a draft study that Dr. Härtl and others, including the visiting researcher, had intended to publish, tracking the fluid’s effectiveness in fusing delicate bones.”
So it seems that Roger Härtl only used the product before there was any warning.
Later, postdoc Dr. Pravesh Gadjradj, who was working with Härtl, reportedly notified his mentor about the FDA warning. What followed sounds pretty awful:
“In the complaint, Dr. Gadjradj said Dr. Härtl requested that he “delete” the research file on the project and “never bring up the topic again.” The researcher said he was concerned that Dr. Härtl had not gone on to inform the patients, according to the complaint, and instead “covered it up.”
The conversation cited in the complaint was in the spring of last year, Dr. Gadjradj said in an interview. In January, after months of worrying about the patients — and believing that they still had not been notified — Dr. Gadjradj lodged the complaint against his boss.”
I believe patients should have been notified about this.
Also, per the NYT piece, it sounds like Weill Cornell is not being very transparent about how it is handling this situation more generally.
A slow, under-resourced FDA?
I also wonder about the institutional IRB and why they didn’t look into this product more carefully even if there wasn’t already FDA action. While FDA guidance on perinatal biologics has evolved often time and hasn’t always been crystal clear, I would think even at the time that the IRB in this case would have been considering the situation it should have been clear that umbilical cord products would be subject to some kind of FDA oversight.
In the bigger picture, part of the problem here is timing.
The FDA is typically very slow to act. Then once it issues a warning (or the weaker “untitled letter”), the agency often takes one or two years to follow up with any particular firm if the agency feels it is still non-compliant. Perhaps the FDA is just understaffed or lacks the necessary resources in the biologics arena. It’d be great to see the CBER branch of the FDA, which handles biologics, get more support.
Burst Biologics is just one of perhaps a dozen or more supplier firms in this biologics space. The FDA, while doing too little on the overall stem cell clinic problem, has been relatively quite active on perinatal suppliers so that’s something positive. I wrote in the spring of last year about the spike in FDA activity in the perinatal arena.
Whether it’s umbilical cord wall or blood products, exosomes, or other perinatal materials, these biological drugs often pose real risks to patients. The main hazard is infection, which goes back to the FDA warnings to the manufacturers where the letters almost always detail problems related to sterility control. For instance, the FDA noted CGMP issues with two BioBurst products in its warning to Burst.
These risks are not just hypothetical as we all learned from the Liveyon disaster, where dozens of patients ended up septic.
Looking ahead: oversight and what’s a drug
Note that the supplier firms sometimes dispute that their products are drugs and push back on FDA oversight. From the NYT piece, we have BioBurst leader Jones in that spirit:
“My business has been warned by F.D.A. of alleged safety concerns with its products related to a regulatory scheme that does not apply to my business,”
The FDA should be the one to define what’s a drug, but federal courts can in a sense overrule the FDA. It’s very rare but one ongoing case highlights that the FDA can be challenged.
Regarding adipose stem cell preps, California federal district court Judge Jesus Bernal ruled against the FDA in the Cell Surgical Network lawsuit. Bernal said an adipose stem cell product, SVF, was not a drug, despite what the FDA determined. That case is now pending appeal with The Ninth Circuit. If the appeal fails, then there will be more uncertainty about whether SVF is a drug. Since the FDA won a similar case and the appeal in Florida, could the pending case end up before SCOTUS? Hopefully, The Ninth Circuit sides with the FDA so things don’t get that far.
I suppose there could be suits over whether perinatal biologics are drugs or not too. Note that an important difference in the birth-related biologics space and the ongoing adipose cell case is that perinatal products are allogeneic, while fat cell preps are used in an autologous manner. Using someone else’s biologics makes those products more likely to be drugs.
Patient rights
Opponents of the FDA and businesses making money off of unapproved biologics often have a mantra that patients have rights to cells. Usually, this is about autologous cells like MSCs sold by so many clinics.
Beyond the question of access to cells, I believe that patients have a right to expect that they will not be given unapproved cellular drug products as though they were standard of care without risks. These drugs usually have no good clinical science behind them either.
Patients should also be notified, even after the fact, if there’s a new concerning event pertaining to what they received. Weill Cornell apparently has not done so.
I’ll end with a quote in the NYT piece from Hank Greely about the Weill Cornell situation:
“The safer thing, the more ethical thing, would be to tell everybody and give them whatever information you’ve got about what’s known about the risks,” said Hank Greely, a law professor at Stanford and director of its Center for Law and the Biosciences. But, he said, doctors and hospitals “are going to be reluctant to do that because they don’t want to look bad, don’t want to attract lawsuits and don’t want to make patients unhappy with them.”
Hank is exactly right on this.
Weill Cornell is not alone. Over the dozen-plus years I’ve been writing here on The Niche I’ve seen too many cases of institutions not doing the right thing in difficult situations related to stem cells or other biologics. They often don’t put patients and transparency first.
Download, open and search for bioburst
https://www.dukehealth.org/sites/default/files/duh-all-op-codes_2020.xlsx
What do insurance companies think they’re paying for? Maybe, just maybe Medicare doesn’t pay for unapproved drugs?
$13K for 1.0 ml. Ouch.
The FDA warning letter to Burst Biologics is truly scary:
1. Failure to determine as ineligible a donor who is identified as having a risk factor for, or clinical evidence of, any of the relevant communicable disease agents or diseases for which screening is required under 21 CFR 1271.75(a)(1) [21 CFR 1271.75(d)(1)]
2. Failure to establish 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)]
3. Failure to have an adequate system for monitoring environmental conditions in an aseptic processing area necessary to prevent contamination or mixups [21 CFR 211.42(c)(10)(iv)]
4. Failure to withhold from use each lot of components, drug product containers, and closures until the lot has been sampled, tested, or examined, as appropriate, and released for use by the quality control unit [21 CFR 211.84(a)].
5. Failure to thoroughly investigate any unexplained discrepancy, or the failure of a batch or any of its components to meet any of its specifications, whether or not the batch has already been distributed [21 CFR 211.192].
To anyone who knows the basics of sterile biological manufacturing, much of the above is terrifying, considering this ‘product’ goes into a human body.
“…about 40 patients at the hospital had received treatment with the fluid under the direction of Dr. Roger Härtl,” Did the treatments work?