Description
We, FDA, are issuing this guidance to provide establishments1 that manufacture human cells, tissues, and cellular and tissue-based products (HCT/Ps) with recommendations for complying with the requirements under Title 21 of the Code of Federal Regulations Part 1271 (21 CFR Part 1271) for investigating and reporting adverse reactions involving communicable disease in recipients of HCT/Ps that are regulated solely under section 361 of the Public Health Service Act (PHS Act) and 21 CFR Part 1271 (hereafter referred to throughout this guidance as “361 HCT/Ps”. In addition, this guidance provides updated information specific to reporting adverse reactions related to HCT/Ps to supplement the general instructions accompanying the MedWatch mandatory reporting form, Form FDA 3500A.
Scope & Applicability
Product Classes
2HCT/Ps regulated solely under section 361 of the PHS Act.; Human Cells, Tissues, and Cellular and Tissue-Based Products regulated solely under section 361 of the PHS Act
Human cells, tissues, and cellular and tissue-based products regulated solely under PHS Act 361; HCT/Ps regulated solely under Section 361 of the PHS Act
Stakeholders
5Entities making donor eligibility determinations
Individual who initially reported the adverse reaction
Recipients of blood components who must be notified of risks
Entity responsible for submitting NDINs
Potential HCT/P donor screening
Regulatory Context
Attributes
2Criterion for regulation under 21 CFR 1271.10(a)
Criterion for regulation under 21 CFR 1271.10(a)
Identified Hazards
Hazards
2Risk of transmission through HCT/P use
Risk associated with construction, traffic flow, and shared equipment.; Risk from raw food to RTE food or from insanitary objects; Personnel handling RTE foods touch contaminated surfaces
Related CFR Sections (14)
- 21CFR600.80§ 600.80 Postmarketing reporting of adverse experiences.
(a) Definitions. The following definitions of terms apply to this section:Read full regulation →
- 21CFR312.32§ 312.32 IND safety reporting.
(a) Definitions. The following definitions of terms apply to this section:Read full regulation →
- 21CFR1271.350§ 1271.350 Reporting.
(a) Adverse reaction reports.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 →
- 21CFR1271.160§ 1271.160 Establishment and maintenance of a quality program.
(a) General. If you are an establishment that performs any step in the manufacture of HCT/Ps, you must establish and maintain a quality program intended to prevent the introduction, transmission, or spread of communicable diseases through the manufacture and use of HCT/Ps. The quality program must bRead full regulation →
- 21CFR1271.320§ 1271.320 Complaint file.
(a) Procedures. You must establish and maintain procedures for the review, evaluation, and documentation of complaints as defined in § 1271.3(aa) , relating to core current good tissue practice (CGTP) requirements, and the investigation of complaints as appropriate.Read full regulation →
- 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 →
- 21CFR1271.150§ 1271.150 Current good tissue practice requirements.
(a) General. This subpart D and subpart C of this part set forth current good tissue practice (CGTP) requirements. You must follow CGTP requirements to prevent the introduction, transmission, or spread of communicable diseases by HCT/Ps (e.g., by ensuring that the HCT/Ps do not contain communicable Read full regulation →
- 21CFR1271.190§ 1271.190 Facilities.
(a) General. Any facility used in the manufacture of HCT/Ps must be of suitable size, construction, and location to prevent contamination of HCT/Ps with communicable disease agents and to ensure orderly handling of HCT/Ps without mix-ups. You must maintain the facility in a good state of repair. YouRead full regulation →
- 21CFR1271.210§ 1271.210 Supplies and reagents.
(a) Verification. You must not use supplies and reagents until they have been verified to meet specifications designed to prevent circumstances that increase the risk of the introduction, transmission, or spread of communicable diseases. Verification may be accomplished by the establishment that useRead full regulation →
- 21CFR1271.195§ 1271.195 Environmental control and monitoring.
(a) Environmental control. Where environmental conditions could reasonably be expected to cause contamination or cross-contamination of HCT/Ps or equipment, or accidental exposure of HCT/Ps to communicable disease agents, you must adequately control environmental conditions and provide proper conditRead full regulation →
- 21CFR1271.260§ 1271.260 Storage.
(a) Control of storage areas. You must control your storage areas and stock rooms to prevent:Read full regulation →
- 21CFR1271.265§ 1271.265 Receipt, predistribution shipment, and distribution of an HCT/P.
(a) Receipt. You must evaluate each incoming HCT/P for the presence and significance of microorganisms and inspect for damage and contamination. You must determine whether to accept, reject, or place in quarantine each incoming HCT/P, based upon pre-established criteria designed to prevent communicaRead full regulation →
- 21CFR1271.250§ 1271.250 Labeling controls.
(a) General. You must establish and maintain procedures to control the labeling of HCT/Ps. You must design these procedures to ensure proper HCT/P identification and to prevent mix-ups.Read full regulation →
Related Warning Letters (10)
- 2025-12-16
CGMP/Deviations/Biologics License Application (BLA)
Microvascular Tissue, Inc.
- 2025-12-16
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Green Valley Fertility Partners
- 2025-12-09
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BioXtek LLC
- 2025-12-09
Unapproved New Drug/Unlicensed Biological Product/Biologics License Application (BLA)
Celularity, Inc
- 2025-12-09
Unapproved New Drug/Unlicensed Biological Product/Biologics License Application (BLA)
Lux Therapeutics LLC dba Ponya Therapeutics LLC
- 2025-10-28
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Royal Philips
- 2025-10-07
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New Life Medical Services, LLC
- 2025-09-30
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Insung Medical Co. Ltd.
- 2025-09-16
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- 2025-08-26
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See Also (8)
- Development and Licensure of Vaccines to Prevent COVID-19: Guidance for Industry (Status: Final)
- Postmarketing Adverse Experience Reporting for Human Drug and Licensed Biological Products: Clarification of What to Report (Status: Final)
- How to Complete the Vaccine Adverse Event Reporting System Form (VAERS-1): Guidance for Industry (Status: Final)
- Postmarketing Safety Reporting for Human Drug and Biological Products Including Vaccines: Draft Guidance for Industry (Status: Draft)
- Evaluating the Risks of Drug Exposure in Human Pregnancies (Status: Final)
- Biological Product Deviation Reporting for Licensed Manufacturers of Biological Products Other than Blood and Blood Components (Status: Final)
- Postmarketing Adverse Event Reporting for Nonprescription Human Drug Products Marketed Without an Approved Application (Status: Final)
- Safety Reporting Requirements for INDs (Investigational New Drug Applications) and BA/BE (Bioavailability/Bioequivalence) Studies: Guidance for Industry and Investigators (Status: Final)