Self-launched 361 commercial “stem cell products”

by Alexey Bersenev on June 23, 2015 · 0 comments

in cell product, regulation

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As you may know, I’m trying to capture all stem cell products available on a market worldwide. I realized that there are two groups of such products – the first is the products, approved by governmental regulatory agencies (usually considered drugs) and the second is so-called self-launched not approved cell/ tissue products. Today, I’d like to discuss some issues, related to second group of commercial “stem cell products”.

Examples of self-launched cell/tissue products:

Common features of these products:

  1. Self-launched by companies. Means there is no marketing approval/ authorization by government agency.
  2. Self-proclaimed as compliant with FDA regulations. But their self-proclaimed compliance is proved to be wrong (by FDA letters) or very questionable.
  3. Product launch on a market and claim of regulatory compliance happen without consulting with FDA.
  4. FDA cracked down on some of these products, claiming that these are in fact 351 products (drugs).
  5. Self-proclaimed as “stem cell products”. Usually means: “contains alive mesenchymal stem cells”.
  6. Almost exclusively used in orthopedics (so-called “orthobiologics”) and for skin repair.
  7. Big companies on orthopedics market love to have them in portfolio (Stryker, NuVasive, Arthrex).
  8. Post-marketing studies on efficacy and cost-effectiveness are very limited.

Regulatory compliance
As I noted above, self-proclaimed regulatory compliance of these product turns out to be a false. In the last 5 years FDA inspected these companies and issued a number of quite similar letters. Some of these letters:

These letters indicate to non-compliant marketing of the products, which misclassified by companies as 361 HCT/P, instead of drugs (351). Interestingly, most of these products stayed on a market (AlloStem, Ovation/ BIO4), despite FDA’s warnings.

Business model
Despite FDA early letters (from Parcell and AlloSource in 2011), the companies continued to do the same thing over and over again in 2013 (Osiris) and in 2014 (RTI Surgical). Very recent deal between Stryker and Osiris on transformation of Ovation into BIO4 is an example of continuing trend. Why didn’t they learn? Did they miss those FDA letters? Did they consult with FDA on classification of their products? Do they actually care at all about FDA’s “current thinking”? NO, NO and NO! It indicates that self-launch and self-claims are working well for a profit. It seem to me, their regulatory compliance people did not do homework or were asked to follow the scheme:
– don’t consult with FDA!
– self-launch it with fancy label “stem cell”!
– pitch it to surgeons – they like to be innovative and “push an envelope”!
– enjoy a ride $$$ until FDA will crack down on you.
Why this business model is still thriving? Well, first of all, FDA may never come to you (they have limited resources) if you don’t kill any patient. Second, if FDA will sniff you, it may take 1-2 years before audit, months for report, 1 year for responses and so on. Third, companies may get away with it by pleasing or negotiating with FDA (Osiris did it for Grafix) – changing marketing language (Biomet removed all osteogenic cells/ MSC-related language from description of Cellentra as advertised earlier in 2012) , narrowing down therapeutic indications, promise to do some post-marketing studies. Another possible model is divesting a product (Osiris sold Osteocel to NuVasive), partnership with big players (Osiris – Stryker deal).

I’d like to give one more example of “changing a marketing language” about products in order to become “pseudo-compliant”. Nutech widely advertised their product “Nucel” as containing amniotic (stem) cells along with amniotic membrane (examples here and here). However, watching FDA cracking down on some 361 products and reading FDA updates (see the first update of 2012 from FDA Tissue Reference Group), they decided to tune up language and removed a mention of “cells” from their web site. Compliance is done? Very simple fix – remove word “cells” from everywhere!

Therapeutic efficacy
There are very little good published clinical data available about efficacy of these products. If we look at orthobiologics, things are not so positive as one may think. For example, the recent report on efficacy of Osteocel (NuVasive) in matched cohort spinal fusion, was negative:

This is the first non-industry sponsored study to analyze a matched cohort assessing the one-year arthrodesis rates associated with a non-structural MSC allograft in one and two-level ACDF procedures. There were no statistically significant differences in fusion rates between the two cohorts.

The recent overview (highly recommended!) of commercially available cellular bone matrices in spinal surgery, came up with the following conclusions:

Although CBMs appear to be safe for use as bone graft substitutes, their efficacy in spinal fusion surgery remains highly inconclusive. Large, nonindustry sponsored studies evaluating the efficacy of CBMs are required. Without results from such studies, surgeons must be made aware of the potential pitfalls of CBMs in spinal fusion surgery. With the currently available data, there is insufficient evidence to support the use of CBMs as bone graft substitutes in spinal fusion surgery.

The situation with 361 “stem cell products” for skin defects is much better. For example, recent report about Grafix efficacy in diabetic foot ulcers.

For physicians:
I hope this post will help physicians to learn something about not approved cell/ tissue products, advertised as “stem cell products”. Please be informed and protect yourself! Try to be innovative, but equip yourself with a knowledge about the product! Do not always trust advertisement! Finally, very good advice you can also find here:

Ask your friendly company representative to provide you with a letter from the company in which they state that the product on offer was discussed with the FDA and the FDA said that they agreed that the product was Section 361 compliant. If you really want to make them sweat, ask them if they have had a response from the Tissue Reference Group.

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