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An unlicensed autologous stem cell product derived from adipose tissue is under Food and Drug Administration scrutiny for manufacturing processes that may compromise its safety and for failing to toe the regulatory line in marketing.

American CryoStem received an FDA warning letter Jan. 3 demanding that the company comply with best-manufacturing processes and obtain an investigational new drug application if it wishes to continue marketing ATCELL for its currently advertised clinical indications and administration routes. These include intravenous, intrathecal, or aerosol inhalation of the product for anoxic brain injury, Parkinson’s disease, amyotrophic lateral sclerosis, stroke, and multiple sclerosis.

Wikimedia Commons/FitzColinGerald/Creative Commons License
The company noted that ATCELL is an investigational product, marketed as being for research only. While that may be true, FDA noted in the warning letter, American CryoStem has not obtained the proper licensure to support the product’s development.

“Please be advised that, to lawfully market a drug that is a biological product, a valid biologics license must be in effect,” noted the letter. “Such licenses are issued only after a showing that the product is safe, pure, and potent. While in the development stage, such products may be distributed for clinical use in humans only if the sponsor has an investigational new drug application (IND) in effect as specified by FDA regulations. ATCELL is not the subject of an approved biologics license application nor is there an IND in effect. Based on this information, we have determined that your actions have violated the Food, Drug, and Cosmetic Act and the Public Health Service Act.”

FDA inspectors conducted a site inspection of American CryoStem in Eatontown, N.J., last summer, during which they “documented evidence of significant deviations from current good manufacturing practice.” The agency then provided the company a chance to respond to these issues. The new warning letter discussed each complaint, noting that some were inadequately addressed, and demanded that the company take action within 15 working days or face potential legal process, including seizure and/or injunction.

American CryoStem is one of the first companies to experience increased scrutiny under FDA’s new commitment to regulate the rapid growth and development of regenerative medicine products, which include novel cellular therapies, with the aim of ensuring their safety and effectiveness.

The new policy is designed to support the potential of cellular rejuvenation medicine, while protecting patients from “unscrupulous actors” who might endanger public health with untested products, according to FDA Commissioner Scott Gottlieb, MD. As enthusiasm for stem cell treatments surges, so are reports of adverse events. The New England Journal of Medicine recently reported on three patients with age-related macular degeneration who were blinded by intravitreal injection of autologous adipose-derived stem cells (N Engl J Med. 2017;376:1047-53).

Under the new policy, cell- and tissue-based products could be exempt from FDA premarket review only if they are removed from and implanted back into the same patient in their original form, or if the products are “minimally manipulated.” ATCELL fulfills neither qualification, the FDA warning letter said.

“You process adipose tissue ... to isolate cellular components of adipose tissue, commonly referred to as stromal vascular fraction [SVF]. Such processing is more than minimal manipulation because [it alters] the original relevant characteristics of the [tissue] relating to its utility for reconstruction, repair, or replacement. Then you process the SVF by expanding it in cell culture to manufacture ATCELL. Such expansion also is more than minimal manipulation because it alters the original relevant characteristics of the tissue.”

Furthermore, the letter noted, at least one of the components used in the clonal expansion process is investigational and not intended for human use. The manufacturer of that component, which was not named, “indicates the following: ‘Unless otherwise stated in our catalog or other company documentation accompanying the product(s), our products are intended for research use only and are not to be used for any other purpose, which includes but is not limited to, unauthorized commercial uses, in vitro diagnostic uses, ex vivo or in vivo therapeutic uses or any type of consumption or application to human and animals.”

The FDA also took exception with several equipment and lab safety issues. ATCELL was being created in areas that had no clean space designation – a serious concern, the letter said.

“American CryoStem’s unvalidated processes, inadequately controlled environment, lack of control of components used in production, and lack of sufficient and validated product testing ... pose a significant risk that ATCELL may be contaminated with microorganisms or have other serious product quality defects ... Because the product is administered to humans by various higher risk routes of administration, including intravenously, intrathecally, and by aerosol inhalation, if contaminated, its use could cause a range of adverse events, from infections to death.”

FDA also expressed concerns over a lack of consistent quality control testing of each batch and questioned whether the company’s method of shipping ATCELL to clinicians had been adequately validated.

Finally, the agency raised concerns that ATCELL, while it is labeled as being for research purposes only, may harm patients indirectly by preventing them from seeking timely treatment with proven therapies.

“ATCELL is intended to treat a variety of serious or life-threatening diseases or conditions, all of which are non-homologous uses,” the warning letter noted. “Such uses raise potential significant safety concerns because there is less basis on which to predict the product’s behavior in the recipient, and use of these unapproved products may cause users to delay or discontinue medical treatments that have been found safe and effective.”

SOURCE: FDA warning letter

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An unlicensed autologous stem cell product derived from adipose tissue is under Food and Drug Administration scrutiny for manufacturing processes that may compromise its safety and for failing to toe the regulatory line in marketing.

American CryoStem received an FDA warning letter Jan. 3 demanding that the company comply with best-manufacturing processes and obtain an investigational new drug application if it wishes to continue marketing ATCELL for its currently advertised clinical indications and administration routes. These include intravenous, intrathecal, or aerosol inhalation of the product for anoxic brain injury, Parkinson’s disease, amyotrophic lateral sclerosis, stroke, and multiple sclerosis.

Wikimedia Commons/FitzColinGerald/Creative Commons License
The company noted that ATCELL is an investigational product, marketed as being for research only. While that may be true, FDA noted in the warning letter, American CryoStem has not obtained the proper licensure to support the product’s development.

“Please be advised that, to lawfully market a drug that is a biological product, a valid biologics license must be in effect,” noted the letter. “Such licenses are issued only after a showing that the product is safe, pure, and potent. While in the development stage, such products may be distributed for clinical use in humans only if the sponsor has an investigational new drug application (IND) in effect as specified by FDA regulations. ATCELL is not the subject of an approved biologics license application nor is there an IND in effect. Based on this information, we have determined that your actions have violated the Food, Drug, and Cosmetic Act and the Public Health Service Act.”

FDA inspectors conducted a site inspection of American CryoStem in Eatontown, N.J., last summer, during which they “documented evidence of significant deviations from current good manufacturing practice.” The agency then provided the company a chance to respond to these issues. The new warning letter discussed each complaint, noting that some were inadequately addressed, and demanded that the company take action within 15 working days or face potential legal process, including seizure and/or injunction.

American CryoStem is one of the first companies to experience increased scrutiny under FDA’s new commitment to regulate the rapid growth and development of regenerative medicine products, which include novel cellular therapies, with the aim of ensuring their safety and effectiveness.

The new policy is designed to support the potential of cellular rejuvenation medicine, while protecting patients from “unscrupulous actors” who might endanger public health with untested products, according to FDA Commissioner Scott Gottlieb, MD. As enthusiasm for stem cell treatments surges, so are reports of adverse events. The New England Journal of Medicine recently reported on three patients with age-related macular degeneration who were blinded by intravitreal injection of autologous adipose-derived stem cells (N Engl J Med. 2017;376:1047-53).

Under the new policy, cell- and tissue-based products could be exempt from FDA premarket review only if they are removed from and implanted back into the same patient in their original form, or if the products are “minimally manipulated.” ATCELL fulfills neither qualification, the FDA warning letter said.

“You process adipose tissue ... to isolate cellular components of adipose tissue, commonly referred to as stromal vascular fraction [SVF]. Such processing is more than minimal manipulation because [it alters] the original relevant characteristics of the [tissue] relating to its utility for reconstruction, repair, or replacement. Then you process the SVF by expanding it in cell culture to manufacture ATCELL. Such expansion also is more than minimal manipulation because it alters the original relevant characteristics of the tissue.”

Furthermore, the letter noted, at least one of the components used in the clonal expansion process is investigational and not intended for human use. The manufacturer of that component, which was not named, “indicates the following: ‘Unless otherwise stated in our catalog or other company documentation accompanying the product(s), our products are intended for research use only and are not to be used for any other purpose, which includes but is not limited to, unauthorized commercial uses, in vitro diagnostic uses, ex vivo or in vivo therapeutic uses or any type of consumption or application to human and animals.”

The FDA also took exception with several equipment and lab safety issues. ATCELL was being created in areas that had no clean space designation – a serious concern, the letter said.

“American CryoStem’s unvalidated processes, inadequately controlled environment, lack of control of components used in production, and lack of sufficient and validated product testing ... pose a significant risk that ATCELL may be contaminated with microorganisms or have other serious product quality defects ... Because the product is administered to humans by various higher risk routes of administration, including intravenously, intrathecally, and by aerosol inhalation, if contaminated, its use could cause a range of adverse events, from infections to death.”

FDA also expressed concerns over a lack of consistent quality control testing of each batch and questioned whether the company’s method of shipping ATCELL to clinicians had been adequately validated.

Finally, the agency raised concerns that ATCELL, while it is labeled as being for research purposes only, may harm patients indirectly by preventing them from seeking timely treatment with proven therapies.

“ATCELL is intended to treat a variety of serious or life-threatening diseases or conditions, all of which are non-homologous uses,” the warning letter noted. “Such uses raise potential significant safety concerns because there is less basis on which to predict the product’s behavior in the recipient, and use of these unapproved products may cause users to delay or discontinue medical treatments that have been found safe and effective.”

SOURCE: FDA warning letter

 

An unlicensed autologous stem cell product derived from adipose tissue is under Food and Drug Administration scrutiny for manufacturing processes that may compromise its safety and for failing to toe the regulatory line in marketing.

American CryoStem received an FDA warning letter Jan. 3 demanding that the company comply with best-manufacturing processes and obtain an investigational new drug application if it wishes to continue marketing ATCELL for its currently advertised clinical indications and administration routes. These include intravenous, intrathecal, or aerosol inhalation of the product for anoxic brain injury, Parkinson’s disease, amyotrophic lateral sclerosis, stroke, and multiple sclerosis.

Wikimedia Commons/FitzColinGerald/Creative Commons License
The company noted that ATCELL is an investigational product, marketed as being for research only. While that may be true, FDA noted in the warning letter, American CryoStem has not obtained the proper licensure to support the product’s development.

“Please be advised that, to lawfully market a drug that is a biological product, a valid biologics license must be in effect,” noted the letter. “Such licenses are issued only after a showing that the product is safe, pure, and potent. While in the development stage, such products may be distributed for clinical use in humans only if the sponsor has an investigational new drug application (IND) in effect as specified by FDA regulations. ATCELL is not the subject of an approved biologics license application nor is there an IND in effect. Based on this information, we have determined that your actions have violated the Food, Drug, and Cosmetic Act and the Public Health Service Act.”

FDA inspectors conducted a site inspection of American CryoStem in Eatontown, N.J., last summer, during which they “documented evidence of significant deviations from current good manufacturing practice.” The agency then provided the company a chance to respond to these issues. The new warning letter discussed each complaint, noting that some were inadequately addressed, and demanded that the company take action within 15 working days or face potential legal process, including seizure and/or injunction.

American CryoStem is one of the first companies to experience increased scrutiny under FDA’s new commitment to regulate the rapid growth and development of regenerative medicine products, which include novel cellular therapies, with the aim of ensuring their safety and effectiveness.

The new policy is designed to support the potential of cellular rejuvenation medicine, while protecting patients from “unscrupulous actors” who might endanger public health with untested products, according to FDA Commissioner Scott Gottlieb, MD. As enthusiasm for stem cell treatments surges, so are reports of adverse events. The New England Journal of Medicine recently reported on three patients with age-related macular degeneration who were blinded by intravitreal injection of autologous adipose-derived stem cells (N Engl J Med. 2017;376:1047-53).

Under the new policy, cell- and tissue-based products could be exempt from FDA premarket review only if they are removed from and implanted back into the same patient in their original form, or if the products are “minimally manipulated.” ATCELL fulfills neither qualification, the FDA warning letter said.

“You process adipose tissue ... to isolate cellular components of adipose tissue, commonly referred to as stromal vascular fraction [SVF]. Such processing is more than minimal manipulation because [it alters] the original relevant characteristics of the [tissue] relating to its utility for reconstruction, repair, or replacement. Then you process the SVF by expanding it in cell culture to manufacture ATCELL. Such expansion also is more than minimal manipulation because it alters the original relevant characteristics of the tissue.”

Furthermore, the letter noted, at least one of the components used in the clonal expansion process is investigational and not intended for human use. The manufacturer of that component, which was not named, “indicates the following: ‘Unless otherwise stated in our catalog or other company documentation accompanying the product(s), our products are intended for research use only and are not to be used for any other purpose, which includes but is not limited to, unauthorized commercial uses, in vitro diagnostic uses, ex vivo or in vivo therapeutic uses or any type of consumption or application to human and animals.”

The FDA also took exception with several equipment and lab safety issues. ATCELL was being created in areas that had no clean space designation – a serious concern, the letter said.

“American CryoStem’s unvalidated processes, inadequately controlled environment, lack of control of components used in production, and lack of sufficient and validated product testing ... pose a significant risk that ATCELL may be contaminated with microorganisms or have other serious product quality defects ... Because the product is administered to humans by various higher risk routes of administration, including intravenously, intrathecally, and by aerosol inhalation, if contaminated, its use could cause a range of adverse events, from infections to death.”

FDA also expressed concerns over a lack of consistent quality control testing of each batch and questioned whether the company’s method of shipping ATCELL to clinicians had been adequately validated.

Finally, the agency raised concerns that ATCELL, while it is labeled as being for research purposes only, may harm patients indirectly by preventing them from seeking timely treatment with proven therapies.

“ATCELL is intended to treat a variety of serious or life-threatening diseases or conditions, all of which are non-homologous uses,” the warning letter noted. “Such uses raise potential significant safety concerns because there is less basis on which to predict the product’s behavior in the recipient, and use of these unapproved products may cause users to delay or discontinue medical treatments that have been found safe and effective.”

SOURCE: FDA warning letter

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