Description
We, the Center for Biologics Evaluation and Research (CBER), FDA, are recommending ways that would allow you, the manufacturer, generally a cord blood bank, to apply for licensure of minimally manipulated, unrelated allogeneic placental/umbilical cord blood, for hematopoietic and immunologic reconstitution in patients with disorders affecting the hematopoietic system that are inherited, acquired, or result from myeloablative treatment. This guidance document is intended to assist you in obtaining a biologics license. It contains information about the manufacture of minimally manipulated, unrelated allogeneic placental/umbilical cord blood and how to comply with applicable regulatory requirements.
Scope & Applicability
Product Classes
2Proper name for minimally manipulated, unrelated allogeneic placental/umbilical cord blood products.; Hematopoietic Progenitor Cells derived from placental/umbilical cord blood; Hematopoietic Progenitor Cells, Cord Blood product intended for reconstitution; The primary product subject to the guidance; Hematopoietic Progenitor Cells derived from umbilical cord blood; hematopoietic progenitor cells derived from cord blood; Hematopoietic Progenitor Cells from cord blood; hematopoietic progenitor ce
Human cells, tissues, or cellular or tissue-based products defined in 21 CFR Part 1271
Stakeholders
8The manufacturer typically responsible for applying for licensure.; Entity utilizing HLA testing laboratories
potential sponsors of IND applications
The receiving distributor who provides an acknowledgment letter.
responsible for all technical aspects of the cord blood bank
responsible for all medical aspects of the cord blood bank
Responsible for ensuring the overall quality of the final drug product.
Covered establishments include contract laboratories.; Entity performing testing only; Entities performing release or stability testing only
Entity responsible for submitting NDINs
Regulatory Context
Attributes
6Criterion for regulation under section 361
Required label element for outsourcing facilities
Records of investigational products should include expiration dates if applicable.
ACTP availability for distribution only after donor eligibility is established
Should be 6 months from the date of collection.; Expiration or use-by period on container label
Measurement of potency for biological products
Identified Hazards
Hazards
4Risks that manufacturing controls are intended to prevent.
Potential for contamination of covered produce; Known or reasonably foreseeable hazards in water
Microorganisms or particulate matter that could adversely affect the device.
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 (20)
- 21CFR600.14§ 600.14 Reporting of biological product deviations by licensed manufacturers.
(a) Who must report under this section?Read full regulation →
- 21CFR601.12§ 601.12 Changes to an approved application.
(a) General.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 →
- 21CFR211.180§ 211.180 General requirements.
(a) Any production, control, or distribution record that is required to be maintained in compliance with this part and is specifically associated with a batch of a drug product shall be retained for at least 1 year after the expiration date of the batch or, in the case of certain OTC drug products lRead full regulation →
- 21CFR211.198§ 211.198 Complaint files.
(a) Written procedures describing the handling of all written and oral complaints regarding a drug product shall be established and followed. Such procedures shall include provisions for review by the quality control unit, of any complaint involving the possible failure of a drug product to meet anyRead full regulation →
- 21CFR600.80§ 600.80 Postmarketing reporting of adverse experiences.
(a) Definitions. The following definitions of terms apply to this section:Read full regulation →
- 21CFR211.192§ 211.192 Production record review.
All drug product production and control records, including those for packaging and labeling, shall be reviewed and approved by the quality control unit to determine compliance with all established, approved written procedures before a batch is released or distributed. Any unexplained discrepancy (inRead full regulation →
- 21CFR1271.290§ 1271.290 Tracking.
(a) General. If you perform any step in the manufacture of an HCT/P in which you handle the HCT/P, you must track each such HCT/P in accordance with this section, to facilitate the investigation of actual or suspected transmission of communicable disease and take appropriate and timely corrective acRead full regulation →
- 21CFR1271.270§ 1271.270 Records.
(a) General. You must maintain records concurrently with the performance of each step required in this subpart and subpart C of this part . Any requirement in this part that an action be documented involves the creation of a record, which is subject to the requirements of this section. All records mRead full regulation →
- 21CFR211.170§ 211.170 Reserve samples.
(a) An appropriately identified reserve sample that is representative of each lot in each shipment of each active ingredient shall be retained. The reserve sample consists of at least twice the quantity necessary for all tests required to determine whether the active ingredient meets its establishedRead full regulation →
- 21CFR211.166§ 211.166 Stability testing.
(a) There shall be a written testing program designed to assess the stability characteristics of drug products. The results of such stability testing shall be used in determining appropriate storage conditions and expiration dates. The written program shall be followed and shall include:Read full regulation →
- 21CFR211.165§ 211.165 Testing and release for distribution.
(a) For each batch of drug product, there shall be appropriate laboratory determination of satisfactory conformance to final specifications for the drug product, including the identity and strength of each active ingredient, prior to release. Where sterility and/or pyrogen testing are conducted on sRead full regulation →
- 21CFR211.160§ 211.160 General requirements.
(a) The establishment of any specifications, standards, sampling plans, test procedures, or other laboratory control mechanisms required by this subpart, including any change in such specifications, standards, sampling plans, test procedures, or other laboratory control mechanisms, shall be drafted Read 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 →
- 21CFR211.150§ 211.150 Distribution procedures.
Written procedures shall be established, and followed, describing the distribution of drug products. They shall include:Read full regulation →
- 21CFR1271.55§ 1271.55 What records must accompany an HCT/P after the donor-eligibility determination is complete; and what records must I retain?
(a) Accompanying records. Once a donor-eligibility determination has been made, the following must accompany the HCT/P at all times:Read full regulation →
- 21CFR201.25§ 201.25 Bar code label requirements.
(a) Who is subject to these bar code requirements? Manufacturers, repackers, relabelers, and private label distributors of a human prescription drug product or an over-the-counter (OTC) drug product that is regulated under the Federal Food, Drug, and Cosmetic Act or the Public Health Service Act areRead full regulation →
- 21CFR610.61§ 610.61 Package label.
The following items shall appear on the label affixed to each package containing a product:Read full regulation →
- 21CFR610.60§ 610.60 Container label.
(a) Full label. The following items shall appear on the label affixed to each container of a product capable of bearing a full label:Read full regulation →
- 21CFR201.56§ 201.56 Requirements on content and format of labeling for human prescription drug and biological products.
(a) General requirements. Prescription drug labeling described in § 201.100(d) must meet the following general requirements:Read full regulation →
Related Warning Letters (10)
- 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.
- 2025-12-16
CGMP/Deviations/Biologics License Application (BLA)
Microvascular Tissue, Inc.
- 2025-12-16
Deviations/CFR/Regulations for Human Cells, Tissues & Cellular Products (HCT/Ps)
Green Valley Fertility Partners
- 2025-12-11
CGMP/Finished Pharmaceuticals/Adulterated
Catalent Indiana, LLC
- 2025-12-09
Unapproved New Drug/Unlicensed Biological Product/Biologics License Application (BLA)
BioXtek LLC
- 2025-12-09
CGMP/Finished Pharmaceuticals/Adulterated
DeVere Manufacturing Inc.
- 2025-12-09
CGMP/Finished Pharmaceuticals/Adulterated
CDL Services, Inc. DBA Technichem
See Also (8)
- Study Data Technical Conformance Guide - Technical Specifications Document (Status: Final)
- PHS Guideline on Infectious Disease Issues in Xenotransplantation: PHS Guideline (Status: Final)
- Developing Medical Imaging Drug and Biological Products Part 2: Clinical Indications (Status: Final)
- FDA Review of Vaccine Labeling Requirements for Warnings, Use Instructions, and Precautionary Information: Guidance for Industry (Status: Final)
- Pharmacogenomic Data Submissions: Guidance for Industry (Status: Final)
- Toxicity Grading Scale for Healthy Adult and Adolescent Volunteers Enrolled in Preventive Vaccine Clinical Trials: Guidance for Industry (Status: Final)
- Considerations for Plasmid DNA Vaccines for Infectious Disease Indications: Guidance for Industry (Status: Final)
- Labeling for Human Prescription Drug and Biological Products — Determining Established Pharmacologic Class for Use in the Highlights of Prescribing Information (Status: Final)