HCT/PHuman Cells, Tissues, and Cellular and Tissue-Based Products
HCT/P — Human Cells, Tissues, and Cellular and Tissue-Based Products — is the FDA umbrella category that includes everything from a piece of demineralised bone to a cord-blood unit to an amniotic membrane patch. What FDA actually means by the term, how the 361 / 351 line is drawn, and what an establishment has to do before a tissue allograft ships.
01What FDA calls an HCT/P
An HCT/P, per 21 CFR 1271.3(d), is an article containing or consisting of human cells or tissues intended for implantation, transplantation, infusion, or transfer into a human recipient. The category sweeps in bone, ligament, tendon, fascia, cartilage, skin, cornea, heart valves, blood vessels, dura mater, amniotic and chorionic membrane, umbilical cord blood, hematopoietic stem cells, semen, oocytes, and embryos — anything sourced from a human donor and put back into a human body, with carve-outs for whole blood components, secreted products like milk, and minimally manipulated bone marrow.
The category exists because pre-2001 these articles were neither classical drugs, nor devices, nor biologics in the BLA sense. Part 1271 created a unified framework that lets most allografts ship under Section 361 of the Public Health Service Act with cGTP and donor-eligibility controls — and forces anything riskier into full Section 351 biologics licensure.
02The 361 / 351 line
Section 1271.10(a) sets four criteria. An HCT/P is regulated solely under Part 1271 (Section 361) only if it meets ALL of:
- Minimally manipulated.
- Intended for homologous use (the same basic function in the donor and recipient).
- Not combined with another article (with limited exceptions for water, crystalloids, sterilising / preservation agents).
- Either has no systemic effect and is not dependent on the metabolic activity of living cells for its primary function; or has a systemic effect / depends on metabolic activity but is for autologous use, allogeneic use in a first- or second-degree blood relative, or reproductive use.
Fail any one of those tests and the HCT/P is a Section 351 biologic — drug, device, or biological product — and the establishment needs an IND for clinical use and a BLA (or 510(k) / PMA) for commercial distribution. CAR-T cells, expanded MSC products, decellularised matrices intended for non-homologous use, and most cosmetic stem-cell products fall on the 351 side.
03Minimal manipulation — what FDA actually means
For structural tissue (bone, ligament, skin), minimal manipulation is processing that does not alter the original relevant characteristics relating to the tissue's utility for reconstruction, repair, or replacement. Cutting, shaping, washing, cleaning, demineralisation, lyophilisation, sterilisation, freezing — generally fine. Grinding bone into particles below a threshold size, denaturing collagen, generating a matrix the donor never had — generally not minimal.
For cells and non-structural tissue (cord blood, amniotic fluid, umbilical cord), minimal manipulation is processing that does not alter the relevant biological characteristics. Density-gradient separation, cell selection, freezing — generally fine. Expansion in culture, activation, genetic modification, differentiation — not minimal.
The 2020 FDA guidance walks through specific examples and is the document every tissue establishment regulatory lead reads cover to cover at least twice a year.
04What an HCT/P establishment has to do
- Register with FDA via FURLS / eHCTERS within 5 days of starting operations, and list each HCT/P annually.
- Make a written donor-eligibility determination under 1271 Subpart C before release.
- Operate to cGTP under 1271 Subpart D — facilities, equipment, environmental controls, process controls, labelling, storage, recovery, distribution, complaints, records.
- Maintain a chain of identity from donor to consignee, retained for at least 10 years.
- Report HCT/P deviations on FDA 3486 within 45 days and adverse reactions on MedWatch within 15 days.
- Maintain a complaint file and a recall procedure.
Frequently asked questions
Q.Is a corneal allograft an HCT/P?+
Yes — and it's regulated solely under Part 1271 (Section 361) provided it's recovered, processed, and distributed as a minimally manipulated tissue for homologous use. Eye banks register with FDA and most are accredited by the Eye Bank Association of America.
Q.Is donated milk an HCT/P?+
No — secreted or extracted human products, including milk and ductal fluid (except semen), are excluded under 1271.3(d)(3). Donor milk banks are regulated as food by FDA, with most US banks accredited by HMBANA.
Q.Is bone marrow an HCT/P?+
Minimally manipulated bone marrow for homologous use by HRSA programs and certain peripheral-blood stem-cell products are excluded from Part 1271 under 1271.3(d)(4). Cord blood, however, is squarely inside Part 1271 — and unrelated allogeneic cord blood units sold for transplantation are licensed under Section 351.
Q.What's the difference between an HCT/P establishment and a tissue bank?+
FDA uses 'establishment'; the industry uses 'tissue bank'. AATB-accredited tissue banks are HCT/P establishments that voluntarily meet AATB Standards in addition to FDA cGTP.
Q.Do reproductive HCT/Ps follow the same rules?+
Mostly — but Subpart C has reproductive-specific donor screening requirements (sexual contact history, additional CMV and chlamydia testing for anonymous donors of viable, leukocyte-rich cells).
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