Two decades have passed since the first skincare product containing human cell-culture-derived biosignals was launched in 2001. TNS Recovery Complex by SkinMedica was the pioneer that established a new class of topical skincare products. TNS and other products in the class contain cytokines & growth factors harvested from laboratory culture of human cells. Whereas TNS contains biosignals obtained from cultured fibroblasts (skin cells from human infant foreskins), most other products are based on the culture of stem cells obtained from bone marrow, adipose tissue (fat), umbilical cord, and even (shocking to us!) human embryos. These products contain bio-signals in the form of “conditioned media” which is the nutrient broth in which cells are cultured after it has undergone ultrafiltration to remove all cells, cell parts, and other debris. Conditioned media contains all the biosignals produced by the specific cell type during culture. The biosignals produced are reflective of the genetic machinery of the cell cultures and identical to what they produce naturally within the human body. There are at least two products we are aware of that contain bio-signals in the form of lysed (“ruptured” or “exploded”) cells. These products therefore contain cells or cell parts in their formulation.
BFT has written extensively about the pros, cons, and ethics of different types of cells used to produce biosignals for these products and invites the reader to use the search function on this blogsite, or click on the links below, to acquaint themselves with prior posts.
NO REPORTED ADVERSE EVENTS FROM TOPICAL BIOSIGNAL PRODUCTS
With a twenty-year history and multiple manufacturers producing topical skincare products containing human biosignals, it is not unreasonable to assume millions of applications of such products have occurred. Some of these products have also been used as topical adjuvants with a variety of controlled traumatic aesthetic procedures including microneedling, radiofrequency microneedling, IPL, laser resurfacing, peels, and others. To be candid, we are aware that our brands, AnteAGE and AnteAGE MD, have been used in such procedures many thousands of times. We are unaware of any significant adverse events with any of our products when used alone or in conjunction with aesthetic procedures. Similarly, we have provided substantial quantities of private label versions of our products to other brand names and have not been informed about any significant adverse event with their usage. Again, this is after many, many thousands of such uses. We are convinced our products under all brand names are exceedingly safe. We are also convinced of the safety of other products in this class. Past and current internet searches confirm this conclusion.
Google Scholar, PubMed, and MedWatch (the FDA adverse event reporting system) searches using keywords – skin, skincare, topical, injury, adverse event, growth factors, cytokines, healing, wound, photodamage, aging – produce innumerable references supportive of the use and benefits of topical human biosignals and none that raise concern. Empirically, many hundreds of thousands, if not millions on uses over two decades, attest to the safety of this technology in skincare.
Skincare products containing biosignals are regulated as cosmetics, for which there is a specific definition. Simply put, a cosmetic is a product used to beautify or alter appearance. The Federal Food, Drug, and Cosmetic Act (FD&C Act) defines cosmetics by their intended use, as products “intended to be rubbed, poured, sprinkled, or sprayed on, introduced into, or otherwise applied to the human body…for cleansing, beautifying, promoting attractiveness, or altering the appearance”
In the United States, the FDA does not pre-approve cosmetic products or ingredients, with the important exception of specific color additives. Firms producing cosmetics are responsible for marketing safe, properly labeled products, avoiding the use of prohibited ingredients; and adhering to limits on restricted ingredients. This all changes in the event of reports of significant adverse events and safety concerns.
This contrasts with regulations pertaining to drugs which the FDA defines “by their intended use, as articles for use in the diagnosis, cure, mitigation, treatment, or prevention of disease” and “articles (other than food) intended to affect the structure or any function of the body of man or other animals”.
Aftermarket monitoring (Post-Market Drug Safety Monitoring) is required for drugs and medical devices in all regulatory markets because Phase I, II, and III testing may be insufficient to uncover rare or idiosyncratic detrimental responses. Adverse event reporting systems are therefore necessary to monitor and tabulate untoward events. Drug approvals may also be rescinded if efficacy in use is not predictable or significant. As data accumulates, approval of a drug or device may be rescinded based on revelations occurring during aftermarket monitoring.
Historical examples of approved drugs that were removed from the market include:
Accutane (isotretinoin), Baycol (cerivastatin), Bextra (valdecoxib), Cylert (peoline), Darvon (proposyphine), DES (diethylstilbestrol), Duract (bromfenac), Ergamisol (levamisole), Hismanal (astemizole), Lotronex (alosetron), Meridia (sibutramine), Merital/Alival (nomifensine), Micturin (terodiline), Mylotarg (gemtuzumab ozogamicin), Omniflox (temafloxacine), Palladone (hydromorphone hydrochloride, extended-release), Permax (pergolide), Pondimoin (fenfluramine), Posicor (mibefradil), Propulsid (cisapride), PTZ/Metrazol (pentylenetetrazol), Quaalude (methaqualone), Raplon (rapacuronium), Raptiva (efalizumab), Raxar (grepafloxacin), Redux (dexfenfluramine), Rezulin (troglitazone), Selacryn (tienilic acid), Seldane (terfenadine), Trasylol (aprotinin), Bioxx (rofecoxib), Xigris (drotecogin alfa), Zelmid (zimedlidine), Zelnorm (tegaserod maleate)
FDA PRONOUNCEMENT AND SUBSEQUENT CONFUSION AMONG PROFESSIONALS
The FDA recently announced pending policy changes pertaining to products that meet the definition of an HCT/P in 21 CFR 1271.3(d). HCT/Ps are defined as articles containing or consisting of human cells or tissues that are intended for implantation, transplantation, infusion, or transfer into a human recipient. Examples of HCT/Ps include “bone, ligament, skin, dura mater, heart valve, cornea, hematopoietic stem/progenitor cells derived from peripheral and cord blood, manipulated autologous chondrocytes, epithelial cells on a synthetic matrix, and semen or other reproductive tissue.” Excluded from this definition are “secreted or extracted human products, such as milk, collagen, and cell factors [….].”
Biosignals (cytokines and growth factors) secreted by cells into nutrient broth during laboratory culture are consistent with the excluded substances designation. Furthermore, conditioned media obtained through ultrafiltration to remove all cells, cell parts and other debris does not meet the definition of “consisting of human cells or tissues that are intended for implantation, transplantation, infusion, or transfer into a human recipient.” Based on definitions alone, it seems clear that the recent FDA notification is not applicable to biosignal containing topical skincare products devoid of cells or tissue. Potential exceptions to which the FDA notification may apply are those mentioned above that contain lysed cells within their formulations.
The primary mission of the FDA is to ensure drugs and devices are efficacious and safe prior to being marketed to the public, and that food is also safe. Regulations stipulate that cosmetics do not require premarket approval but must be safe and properly labeled so as not to endanger or deceive the public.
LONG HISTORY OF SAFETY AND EFFICACY OF BIOSIGNAL CONTAINING TOPICAL PRODUCTS
Human biosignal containing skincare products have been used for years in a variety of clinical settings, by physicians and estheticians. In addition to being resold to patients and clients for daily home use, thousands of practitioners have regularly and routinely used these products in their practices. These products have proved valuable in promoting improvements in appearance following a variety of minimally invasive and controlled traumatic procedures. Safety and efficacy of this class of products has been confirmed in many published studies, and as recounted above, in countless instances of use over the course of twenty years. It is your BFT hosts’ opinion that the recently proposed FDA policy implementation is not relevant or applicable to this class of topical skincare products.
An Assessment of Microneedling with Topical Growth Factors for Facial Skin Rejuvenation: A Randomized Controlled Trial. J Clin Aesthet Dermatol. 2020 Nov; 13(11): 22-27
Skin rejuvenation using cosmetic products containing growth factors, cytokines, and matrikines: a review of the literature. Clin Comet Investig Dermatol. 29016; 9:411-419
The potential of topical and injectable growth factors and cytokines for skin rejuvenation. Facial Plast Surg. 2014 Apr;30(2):157-7