Will FDA Regulate PRP Like a Drug?

Will FDA Regulate PRP Like a Drug?

Right now PRP machine manufacturers have registered their machines as 510K cleared medical devices, a much, much less expensive process than if PRP were a drug that required an IDE/BLA and need to be approved by indication (easily 100M per indication). In fact, if these devices required an IDE, you wouldn't be using PRP right now. This past month a few things have happened that have made me think we could see a sea change soon. First, a colleague tried to get a simple knee OA study approved by a VA IRB and was told that he had to call FDA (this was due to the ignorance of the IRB). The FDA proceeded to tell him that as a physician he would need an IDE to do the study (i.e they classified it as a device that is high risk or produces a drug). In addition, he was told that if he activated the PRP with Calcium Chloride, he would have to have a new drug approval (BLA)). I've written an article on this in the past, that technically, activation of PRP places it in the same drug category as culturing, seehttp://www.ncbi.nlm.nih.gov/pubmed/?term=prp+drug+centeno .Finally, a blogger reported this week that a recent cell therapy conference took on Point of Care processing devices (like PRP), see http://stemcellassays.com/2013/10/trends-clinical-point-of-care-cell-processing-devices/#!. One of his conclusions were that the devices were a "threat" to "compliant" cell therapies (by which he means those therapies that seek a biologics/drug license and extensive FDA trials before approval for an indication). Thoughts?

Trends in clinical use of point-of-care cell processing devices stemcellassays.com

One of my favorite workshops at the recent ISCT North America regional meeting was a point-of-care cell processing devices. The topic is very hot and capturing a lot of attention in cell therapy field. In this post, I’m going to...


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Trends in clinical use of point-of-care cell processing devices

by ALEXEY BERSENEV on OCTOBER 9, 2013 · 0 COMMENTS

in REGENMED DIGEST


One of my favorite workshops at the recent ISCT North America regional meeting was apoint-of-care cell processing devices. The topic is very hot and capturing a lot of attention in cell therapy field. In this post, I’m going to summarize some important points which were discussed during this workshop and highlight the current trends. The panel of this workshop included: Lee Buckler (Cell Therapy Group), Brian Barnes (Arteriocyte) and Yong Fan (FDA).

Definitions:
Point-of-care (POC) cell therapy is a process of collecting, processing and administering the cells within one medical procedure. Usually it takes few hours (form 1-2 to 24) and highly depends on processing, type of cells and patient’s condition. There is a great variety of POC devices for cellular therapy, which can be used in different steps of processing: collection (ex: apheresis – Amicus), separation (ex: magnetic with antibody – ClinMACS or by gradient centrifugation – Sepax2), formulation (ex: mixing cells and scaffold before administration – INSTRUCT), post-manufacturing manipulations (ex: washing – Sepax) and delivery of the cells.

Lee Buckler’s reviewed 43 POC cell therapy devices, available on the markets worldwide. The main tissue sources for cell processing were adipose, bone marrow, and peripheral blood. The main output cell products composed of adipose-derived cells, platelet-rich plasma (PRP) and mononuclear cells (blood, bone marrow).

Advantages:
Clearly, POC cell therapy has a lot of advantages, such as:
rapid,
could be done as a practice of medicine;
deal with autologous cells;
could fit in minimal manipulation;
short regulatory path to approval, usually does not require IND/ clinical trials, GMP processing and BLA;
very cheap (done during a day, lack of release assays, lack of quality control, low regulatory burden.

What we should realize is that POC cell processing can potentially deliver 50-100 times cheaper product, compared to conventional cellular therapy (cultured cells in GMP, underwent clinical trials…) with comparable efficacy. For example, cardiac trials by Cytori or use of PRP in sport medicine. Consequently, POC cell therapy could potentially knockout a business of many compliant cell therapy industry companies on the market.

Regulatory issues:
Lee Buckler brought very important issues to discuss. “Used in the clinic” term does not necessarily mean approved, legal and compliant with current regulation. Many companies, marketing POC processing devices, pretend that FDA does not exist. Buckler estimates that roughly half of cell processing devices on US market don’t have any FDA clearance. And surgeons totally fine with it! “Such aggressive marketing matches surgeon’s appetite for innovation” – he said. As a consequence, he sees a great risk when plastic surgeons administer adipose-derived cells in more than dozen unrelated conditions, such as Parkinson’s disease, diabetes or multiple sclerosis. He mentioned, that the lack of enforcement from regulators on the companies, which are placing POC devices on a market without approval, creates a double standard.

Indeed, there is some uncertainty from regulators on POC cell therapy devices. It could be simply regulated as medical device (510k, humanitarian device exemption), but also, as a “biologic” (BLA). As Brian Barnes pointed out, the confusion caused by the variety of POC devices, some of which could not be clearly classified and regulated as: “not device” (does not fit in definition and intended more than for diagnosis), “not drug” (if it’s clearly device) or “not biologic” (if focus on cell collection and delivery). On the other hand, everything could change if regulation is focusing not on a device but on its output. Lee Buckler said: “Where the device is processing and outputting a biologic that line is blurring”.

Yong Fan of FDA admitted some POC devices, such as PRP makers is a very “gray area” and both sides (developer and regulator) are responsible for clarity. She stated that regulation path is very much depends on what goes into device, what happen during processing and what is output. She said that, based on companies marketing claims (use growth factor, activation cells by light, stem cells as output…), most of them (if not all) should submit data and consult with FDA.

More trends:
POC cell therapy is a serious threat to compliant conventional cell therapy in terms of sharing the market due to extremely low cost, potential wide affordability coupled with equal therapeutic efficacy profile.
POC cell therapy field itself is very competitive. Some companies choose to invest a lot of money in pre-clinical studies, comply with FDA and conduct clinical trials (ex: Arteriocyte with Magellan PRP device), but the others can simply use their data for marketing and pretend that FDA does not exist.
Uncertainty, loopholes and lack of enforcement in regulation of POC cell processingallow to “self-designate” device and place it on a market without FDA approval.
Regulation of POC cell therapy may be very different from country to country.
There is a big problem with release criteria for POC cellular products. Surgeons don’t perform/ wait sterility tests. Most physicians don’t do any assays (viability, cell identity by flow cytometry…) before administering the cells after POC processing. It’s unclear how to deal with it and what standards to apply.

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Related posts:
Point-of-care cell processing devices in clinical trials
Cell processing devices in cell therapy – collaboration in Google Wave
Clinical cell processing news – part 1
Clinical cell processing news – part 3, 2013
Clinical cell processing news – part 1, 2013




http://www.ncbi.nlm.nih.gov/pubmed/?term=prp+drug+centeno#!

J Cosmet Dermatol. 2011 Sep;10(3):171-3. doi: 10.1111/j.1473-2165.2011.00575.x.
Is cosmetic platelet-rich plasma a drug to be regulated by the Food and Drug Administration?
Centeno CJ, Fuerst M, Faulkner SJ, Freeman M.

Source

The Centeno-Schultz Clinic, 403 Summit Blvd., Sutie 201, Broomfield, CO 80021, USA. centenooffice@centenoschultzclinic.com

Abstract


In the area of cosmetic dermatology, some physicians have been injecting activated platelet-rich plasma into the face to promote cosmesis or using it to enhance fat grafts. However, subtle changes to the federal drug code (21 CFR 1271.1) made in 2004, when applied to activated PRP, purport to make this autologous substance a federally regulated drug requiring an extensive and costly Biologics License Application. Are autologous cells drugs? Many physicians believe there are significant problems with this regulatory paradigm.

© 2011 Wiley Periodicals, Inc.
PMID: 21896126 [PubMed - indexed for MEDLINE]