Contains Nonbinding Recommendations
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exercise enforcement discretion under limited conditions with respect to the investigational new
drug (IND) application and premarket approval (biologics license application (BLA))
requirements, for certain HCT/Ps. The current version of this guidance explains that FDA intends
to exercise such enforcement discretion for a longer period of time: through May 2021.
The November 2017 version of the guidance finalized the document entitled “Minimal
Manipulation of Human Cells, Tissues, and Cellular and Tissue-Based Products (HCT/Ps); Draft
Guidance for Industry and Food Administration Staff” dated December 2014, and “Homologous
Use of Human Cells, Tissues, and Cellular and Tissue-Based Products (HCT/Ps); Draft Guidance
for Industry and FDA Staff” dated October 2015. It also finalized certain material related to
adipose tissue that was included in draft guidance entitled “Human Cells, Tissues, and Cellular
and Tissue-Based Products (HCT/Ps) from Adipose Tissue: Regulatory Considerations; Draft
Guidance for Industry” dated December 2014 (Adipose Draft Guidance). This material, together
with the material related to adipose tissue included in the final guidance entitled “Same Surgical
Procedure Exception under 21 CFR 1271.15(b); Questions and Answers Regarding the Scope of
the Exception” dated November 2017, superseded the Adipose Draft Guidance. Accordingly, we
did finalize the Adipose Draft Guidance, and that draft guidance was withdrawn in November
2017. Finally, the November 2017 version of the guidance superseded the document entitled
“Minimal Manipulation of Structural Tissue (Jurisdictional Update); Guidance for Industry and
FDA Staff” dated September 2006 (2006 Guidance).
In general, FDA’s guidance documents,including this guidance, do not establish legally
enforceable responsibilities. Instead, guidances describe FDA’s current thinking on a topic and
should be viewed only as recommendations, unless specific regulatory or statutory requirements
are cited. The use of the word should in FDA’s guidances means that something is suggested or
recommended, but not required.
II. BACKGROUND
HCT/Ps are defined in 21 CFR 1271.3(d) as articles containing or consisting of human cells or
tissues that are intended for implantation, transplantation, infusion, or transfer into a human
recipient.
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Because of the unique nature of HCT/Ps, FDA proposed and in 2005 implemented a
tiered, risk-based approach to the regulation of HCT/Ps. Although FDA is authorized to apply
4
Examples of HCT/Ps include, but are not limited to, 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. The following articles are not
considered HCT/Ps: (1) Vascularized human organs for transplantation; (2) Whole Blood or blood components or
blood derivative products subject to listing under 21 CFR Parts 607 and 207, respectively; (3) Secreted or extracted
human products, such as milk, collagen, and cell factors, except that semen is considered an HCT/P; (4) Minimally
manipulated bone marrow for homologous use and not combined with another article (except for water, crystalloids,
or a sterilizing, preserving, or storage agent, if the addition of the agent does not raise new clinical safety concerns
with respect to the bone marrow); (5) Ancillary products used in the manufacture of HCT/P; (6) Cells, tissues, and
organs derived from animals other than humans; (7) In vitro diagnostic products as defined in 21 CFR 809.3(a); and
(8) Blood vessels recovered with an organ, as defined in 42 CFR 121.2 that are intended for use in organ
transplantation and labeled “For use in organ transplantation only” (21 CFR 1271.3(d)).
Please note, the regulatory status of products identified as not being HCT/Ps is beyond the scope of this guidance.