U.S. Food & Drug Administration 

10903 New Hampshire Avenue

Silver Spring, MD 20993 

www.fda.gov

December 20, 2018

UPS EXPRESS MAIL

RECIPIENT NAME

AND ADDRESS

To Whom It May Concern:

It has come to the attention of the United States Food and Drug Administration (FDA or 

the Agency), Center for Biologics Evaluation and Research (CBER), Office of Compliance 

and Biologics Quality (OCBQ) that you appear to be offering “stem cell” products to treat 

a variety of diseases or conditions. FDA generally regulates such products under the 

Public Health Service Act (PHS Act) as human cells, tissues, or cellular or tissue-based 

products (HCT/Ps), as defined in 21 CFR 1271.3(d). Although generally regulated as 

HCT/Ps, such products may also be regulated under the PHS Act and the Federal Food, 

Drug, and Cosmetic Act (FD&C Act), as biological products, drugs, and/or devices, and 

may require pre-market review.1 

FDA’s November 2017 comprehensive regenerative medicine policy framework is 

intended to spur innovation and efficient access to safe and effective regenerative 

medicine products, including HCT/Ps. An overview of the framework is outlined in a 

suite of four guidance documents that are available on FDA’s website at 

https://www.fda.gov/BiologicsBloodVaccines/CellularGeneTherapyProducts/ucm58521

8.htm.

FDA’s final guidance, Regulatory Considerations for Human Cells, Tissues, and Cellular 

and Tissue-Based Products: Minimal Manipulation and Homologous Use, issued in 

November 2017, informed manufacturers, health care providers, and other interested 

parties about the Agency’s compliance and enforcement policy for these products. The 

guidance outlined FDA’s intent to exercise enforcement discretion for the first 36 

months following issuance of the guidance for certain products with respect to FDA’s 

IND and premarket approval requirements when the use of the product does not raise 

reported safety concerns or potential significant safety concerns. This period provides 

manufacturers time to comply with the IND and premarket approval requirements and 

engage with FDA to determine whether they need to submit an IND or marketing 

authorization application, and if so, to submit their application to FDA. 

 1 For example, in order to lawfully market an HCT/P that is also a biological product and 

a drug, a valid biologics license must be in effect. Such licenses are issued only after a 

showing of safety and efficacy for the product’s intended use. While in the development 

stage, such products intended for clinical use in humans, generally require an 

investigational new drug application (IND).
Page 2 – RECIPIENT NAME

FDA is currently applying a risk-based approach to enforcement, accounting for how 

products are being administered and the diseases and conditions for their use, and 

reminds you that the 36-month period during which FDA intends to exercise 

enforcement discretion will end in November 2020.2

Manufacturers, health care providers, and other interested parties who have any 

uncertainty regarding the regulatory status of their products, and who have not already 

done so, are encouraged to contact FDA well in advance of November 2020, to determine 

whether their products are subject to the agency’s premarket approval requirements. 

For more information on how to contact FDA to obtain a recommendation or decision 

regarding the classification of an HCT/P, or for further information about IND 

requirements for biological products, please see pages 23 and 24 of the guidance entitled 

Regulatory Considerations for Human Cells, Tissues, and Cellular and Tissue-Based 

Products: Minimal Manipulation and Homologous Use, available at 

https://www.fda.gov/BiologicsBloodVaccines/CellularGeneTherapyProducts/ucm58521

8.htm.

Sincerely,

Mary A. Malarkey

Director

Office of Compliance and Biologics Quality

Center for Biologics Evaluation and Research

 2 Please be advised that FDA has not evaluated the application of the compliance and 

enforcement policy to your firm or its products. You and your firm are responsible for 

ensuring full compliance with the PHS and FD&C Acts and all applicable regulations.