Celltex FDA FOIA Letter #3 Raises Key New Questions

This is the fourth post in a series I’m doing on an FOIA release of letters between Texas stem cell clinic Celltex and the FDA.

The first three posts, which include helpful background and discussion of other FOIA material from Celltex, can be found here, here, and here.

Today’s post is focused on a newly released May 18, 2012 letter from Celltex to the FDA.

The letter was written to the FDA in response to the inspection of Celltex by FDA officials Joel Martinez and Linda Hoover. To my knowledge this is the first time this letter has been in the public domain.

Celltex letter 3 topAs with each of the FOIA letters, Celltex claimed this one was exempt from public disclosure via FOIA as well. Nonetheless the FDA released it in redacted form about half a year after my initial FOIA request in late 2011.

What’s in this partially redacted 23-page letter?

There’s a lot of boiler plate verbiage that we are by now used to hearing from Celltex, but there is also quite a bit of new information and implications that escaped the redaction.

Celltex begins the letter by yet again arguing that its stem cells are not drugs and are safe.

Soon thereafter they describe the procedural setup and operation by their partner at that time, RNL Bio. They are no longer partners and are in fact suing each other.

Remarkably, as was partially revealed in the past by Celltex itself, RNL Bio was operating a clinic in Texas for Celltex that was like a little piece out of Seoul, Korea.

Essentially all the SOPs were written in Korean and this newly released letter reveals that the RNL Lab operated entirely in Korean, which I take to mean that English by and large was not spoken there.

“…staff perform all the lab operations in Korean….”

It is astonishing to me that Celltex leadership would establish this arrangement whereby they would seem to risk being left in the dark linguistically as to what the heck was going on in the lab processing their patients’ samples.

I wonder if Celltex patients knew about this?

The Korean lab in the heart of Texas clearly posed major challenges for Celltex. In one part of the letter they describe how they were working on this issue:

“To facilitate future visits from the FDA, Mr. Park is taking an English program to strengthen his communication skills and will be using English more regularly in conversation with Celltex leadership.”

It seems to me that efforts at better communication should have been well underway prior to the company treating any patients. Major communication problems in a clinical lab prepping samples for transplantation into human patients in my opinion raises risks for those patients of mixups or other problems.

Celltex goes on to describe a series of new hires in the works that would help them with compliance issues. Again, in hindsight to me it seems that these hires should have been made before the company began any clinically-related operations.

The bulk of the letter is then taken up by Celltex systematically trying to respond to each of the FDA observations in the 483 inspection report. Repeatedly Celltex indicates how it is revising various SOPs and other elements to resolve FDA concerns.

The word “revising” or “revised” becomes like a mantra as you read the letter.

Celltex also seems to repeatedly invoke the idea that the lab in Sugar Land, Texas is doing things just as RNL Bio did them in Korea as though the FDA would be reassured by that.

Celltex Observation 6

For example it seems in the redacted passage immediately above that they are most likely arguing that RNL in Korea likes to keep their equipment for processing human clinical samples for transplantation on the floor so that should be OK for Celltex to do here in the US too. To me that seems like a poor argument. Plus the idea that they clean the floor really really well does not exactly reassure me about keeping equipment on the floor.

More broadly, it also makes me wonder what else that RNL did in Korea that would seem like not the best SOP.

Also keep in mind that even as Celltex was facing all of these issues related to safety and good lab practices raised by the FDA and was scrambling to resolve them, large numbers of patients had already earlier been infused with Celltex stem cells produced under these less-than-ideal lab conditions.

Some other issues crop up as well that I think are notable.

Celltex FOIA letters

For example, in the passage above in response to subsection “C” of observation 1 about validation, the identities of the locations and specific labs used by Celltex/RNL Bio for assaying the Celltex patient stem cells “in the interim” while Celltex was trying to get things shipshape in Texas are redacted. Other portions of the letter have locations redacted as well.

Where the heck were these steps taking place if not at the Sugar Land lab?

Were cells shipped across state lines to a potential RNL Bio/Human Biostar facility in Maryland without an IND or is it possible that samples of the cells went all the way to Korea for analysis?

I am just guessing here due to the redactions, but I suspect the latter is what happened and the cells most likely were sent to Korea.

In either case, there are numerous regulatory and legal issues that might be raised.

In fact, it is quite possible to this day right now that some Celltex patient cells are in multiple locations that the patients do not know about and the cells are out of the chain of command. If that is true, nobody knows what might be done with these patient cell samples that are out of the control of Celltex. For example, some third party could grow them up as an allogeneic product to be sold.

We also have to keep in mind that Celltex’s former partner, RNL Bio, is facing many accusations and troubles.

Bottom line. As we read in this newly released May 2012 letter about the Celltex response to each of the eight FDA observations, in my opinion the content indicates that Celltex jumped the gun on starting clinical operations.

After the fact in response to the FDA they did many positive things so that’s good. But they should have taken these critical steps in advance of starting clinical operations: compliance training, compliance validation, hiring of appropriate personal with needed scientific and regulatory expertise, resolving major language barriers, getting their lab to be compliant, and more.

In the end, in my opinion the way things played out was unnecessarily haphazard for the company and increased risk for both its patients and Celltex investors.

It’s tempting to speculate where Celltex would be today if it had taken the needed time to do all the proper things prior to starting clinical operations in 2011 and had talked to the FDA in advance, filed an IND perhaps as early as 2010, and so forth. We’ll never know, but I believe the company would most likely now be well on the road to being a compliant, productive, and profitable stem cell company operating just here in the US.

Instead, exactly where the company stands today remains unknown and it is unclear if they are conducting clinical operations in Mexico as they had once indicated was their future plan.

2 thoughts on “Celltex FDA FOIA Letter #3 Raises Key New Questions”

  1. How come this blog doesn’t ever push positive developments in the stem cell field in relation to helping patients, sooner?

    BrainStorm’s NurOwn Cell Therapy Receives Orphan Drug Designation in the European Union for ALS

    BrainStorm’s NurOwn Cell Therapy Receives Orphan Drug Designation inthe European Union for ALS

    NEW YORK, NY and PETAH TIKVA, ISRAEL, Jul 29, 2013 (Menafn – Marketwired via COMTEX) –BrainStorm Cell Therapeutics (otcqb:BCLI), a leading developer ofadult stem cell technologies for neurodegenerative diseases, todayannounced that the European Commission has granted Orphan DrugDesignation for NurOwn(TM), the Company’s stem cell therapyconsisting of autologous bone marrow-derived mesenchymal stromalcells secreting neurotrophic factors, for the treatment ofAmyotrophic Lateral Sclerosis (ALS), also known as Lou Gehrig’sDisease. NurOwn received Orphan Drug Designation from the Food andDrug Administration (FDA) in 2011.

    Orphan drugs benefit from 10 years market exclusivity in the EuropeanUnion (EU) after marketing approval. Additional benefits for sponsorcompanies include reduced fees for various centralized activitiesincluding applications for marketing authorization, inspections andprotocol assistance, as well as possible eligibility for EU grantsand other R&D-supporting initiatives.

    BrainStorm is currently conducting a Phase IIa dose-escalating trialwith 12 ALS patients at the Hadassah Medical Center in Jerusalem,Israel. The company anticipates launching a Phase II multi-centertrial at three leading institutions in the United States towards theend of 2013, pending FDA approval.


  2. Pingback: News and Blog Roundup 27/07/13 | Stu's Stem Cell Blog

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