Description
We, FDA, are providing you, human cells, tissues, and cellular and tissue-based product (HCT/P) manufacturers, healthcare providers, and FDA staff, with our current thinking on the criteria under Title 21 of the Code of Federal Regulations (CFR) Part 1271, specifically the 21 CFR 1271.10(a)(1) criterion of minimal manipulation and the 21 CFR 1271.10(a)(2) criterion of homologous use.
Key Topics
Terms and concepts identified from this document
Scope & Applicability
Product Classes
7Human cells, tissues, or cellular or tissue-based products defined in 21 CFR Part 1271
HCT/Ps are the primary products covered by this guidance.; Guidance regarding the reduction of HBV transmission risk in HCT/Ps.; Products for which HBV transmission risk recommendations are provided
Products combining drug, device, or biological constituents; Generally recommended for Enhanced Documentation; Requires 14971-based framework incorporating ICH Q9; A drug-device combination where the device constituent part detects ingestion.
Human cells, tissues, and cellular and tissue-based products regulated as devices; Human cells, tissues, and cellular and tissue-based products regulated as medical devices; Human Cell, Tissue or Cellular or Tissue-Based Product
Tissue that provides physical support, reconstruction, repair, or replacement; Tissues that physically support, serve as a barrier, conduit, connect, cover, or cushion
Cells or tissues regulated based on biological characteristics
Tissues that serve metabolic or other biochemical roles
Stakeholders
3Entity responsible for submitting NDINs
User role with specific access privileges
Users of HCT/Ps in patients
Regulatory Context
Regulatory Activities
6Investigational New Drug submissions
Process to obtain a formal classification determination
Rule does not apply to products marketed under an NDA
PMA application for high-risk devices
Biologics License Application
Consistency and predictability in the premarket review process
Document Types
1Cybersecurity information should be included in device labeling
Attributes
7Criterion for determining regulatory pathway
Key search term and scientific factor for evaluation.
Key tests for vaccine purity should be validated
Relevant biological characteristic of stem cells
Original relevant characteristic of ligament
Primary function dependency for living cells
Properties of tissue in the donor that contribute to its function
Technical Details
Substances
10Specific tissue type discussed regarding regulatory considerations; Considered a structural tissue providing cushioning and support; Structural tissue providing cushioning and support; Tissue used for cushioning, support, and energy storage
Blood product excluded from HCT/P definition
Cells that serve metabolic or biochemical roles; HCT/P used for replenishing the lymphohematopoietic system
Structural tissue used for load-bearing functions
Example of a structural HCT/P
Infused fluids that can contribute to plasma dilution.; infusion volume considered in plasma dilution algorithm
Structural tissue serving as a barrier; Tissue used for barrier, protection, or covering functions
HCT/P type requiring AFB culture
Structural tissue serving as a protective covering
HCT/P product with specific regulatory classification factors
Processes
8The process for which all components must be listed
Regulatory threshold for HCT/P classification
Processing of adipose tissue to isolate cellular components
Processing method for mobilized peripheral blood apheresis products
If cryopreservation poses a risk, potency assays should be performed after this step.
Activity that triggers the requirement for facility registration.
Removal of cells from structural tissue
Physical modification that does not result in chemical alteration.; A process that does not typically chemically alter an ingredient
Clinical Concepts
5Clinical condition where pericardium may be used as a wound covering
Condition where cord blood infusion is considered non-homologous
For studies in which the outcome or outcomes of interest (e.g., myocardial infarction or stroke) include fatal outcomes.
Repair, reconstruction, replacement, or supplementation of a recipient’s cells or tissues with an HCT/P that performs the same basic function
Treatment resulting in the need for hematopoietic stem cell replacement
Identified Hazards
Hazards
1Prevention of introduction, transmission, and spread
Related CFR Sections (3)
- 21CFR1271.10§ 1271.10 Are my HCT/P's regulated solely under section 361 of the PHS Act and the regulations in this part, and if so what must I do?
(a) An HCT/P is regulated solely under section 361 of the PHS Act and the regulations in this part if it meets all of the following criteria:Read full regulation →
- 21CFR1271.3§ 1271.3 How does FDA define important terms in this part?
The following definitions apply only to this part:Read full regulation →
- 21CFR1271.15§ 1271.15 Are there any exceptions from the requirements of this part?
(a) You are not required to comply with the requirements of this part if you are an establishment that uses HCT/P's solely for nonclinical scientific or educational purposes.Read full regulation →
Enforcement Impact
Deficiencies cited in Warning Letters referencing the same regulations
Recent Cases
- 2026-02-24
Unapproved New Drugs/Unlicensed Biological Product Violations
Dynamic Stem Cell Therapy
- 2026-02-24
CGMP/Finished Pharmaceuticals/Adulterated
AQ USA Inc., d.b.a Ross Healthcare Inc.
- 2026-02-24
Compounding Pharmacy/Adulterated Drug Products
MedisourceRx
- 2026-02-24
CGMP/Finished Pharmaceuticals/Adulterated
A. Nelson & Co. Ltd.
- 2026-02-17
CGMP/Finished Pharmaceuticals/Adulterated
Cosmetic Manufacturers Pty Ltd.
Related Warning Letters (10)
- 2026-02-24
Unapproved New Drugs/Unlicensed Biological Product Violations
Dynamic Stem Cell Therapy
- 2026-02-24
CGMP/Finished Pharmaceuticals/Adulterated
AQ USA Inc., d.b.a Ross Healthcare Inc.
- 2026-02-24
Compounding Pharmacy/Adulterated Drug Products
MedisourceRx
- 2026-02-24
CGMP/Finished Pharmaceuticals/Adulterated
A. Nelson & Co. Ltd.
- 2026-02-17
CGMP/Finished Pharmaceuticals/Adulterated
Cosmetic Manufacturers Pty Ltd.
- 2025-12-23
In Vivo Bioavailability-Bioequivalence Studies – Clinical
Maria A. Carballosa, M.D.
- 2025-12-23
CGMP/Finished Pharmaceuticals/Adulterated
SV Labs Corporation
- 2025-12-23
CGMP/Finished Pharmaceuticals/Adulterated
Guangdong Renhe Guozhuang Biotechnology Co., Ltd.
- 2025-12-23
CGMP/Finished Pharmaceuticals/Adulterated
Medinatura New Mexico, Inc.
- 2025-12-16
CGMP/Finished Pharmaceuticals/Adulterated
Sklar Personal Care Inc.
Related MFDS Guidelines
Korean regulatory guidelines covering similar topics
See Also (8)
- Classification of Products as Drugs and Devices and Additional Product Classification Issues: Guidance for Industry and FDA Staff (Status: Final)
- Validation of Procedures for Processing of Human Tissues Intended for Transplantation: Guidance for Industry (Status: Final)
- Recommendations for Obtaining a Labeling Claim for Communicable Disease Donor Screening Tests Using Cadaveric Blood Specimens from Donors of Human Cells, Tissues, and Cellular and Tissue-Based Products (HCT/Ps): Guidance for Industry (Status: Final)
- Assessing Donor Suitability and Blood and Blood Product Safety in Cases of Known or Suspected West Nile Virus Infection: Guidance for Industry (Status: Final)
- Compliance with 21 CFR Part 1271.150(c)(1) – Manufacturing Arrangements: Guidance for Industry (Status: Final)
- Eligibility Determination for Donors of Human Cells, Tissues, and Cellular and Tissue-Based Products: Guidance for Industry (Status: Final)
- Content and Review of Chemistry, Manufacturing, and Control (CMC) Information for Human Somatic Cell Therapy Investigational New Drug Applications (INDs): Guidance for FDA Reviewers and Sponsors (Status: Final)
- Providing Regulatory Submissions in Electronic Format – Drug Establishment Registration and Drug Listing (Status: Final)