Description
"Computer crossmatch" is a process used to ensure that blood released for transfusion is compatible with the intended recipient.1We, FDA, are issuing this guidance to assist you, blood establishments that perform compatibility testing using a computer crossmatch system to perform computerized matching of blood, consistent with current good manufacturing practice (CGMP) requirements in 21 CFR Parts 210, 211 and 606. Blood establishments must have standard operating procedures (SOPs) "to demonstrate incompatibility between the donor’s cell type and the recipient’s serum or plasma type" under the compatibility testing requirements in21 CFR 606.151(c). This guidance describes practices that we believe satisfy the requirements in 21 CFR 606.151(c) to help ensure detection of an incompatible crossmatch when using a computerized system for matching a donor’s cell type with a recipient’s serum or plasma type.
Scope & Applicability
Product Classes
2Products for which computer crossmatch systems may be restricted.
Requires analytical comparability per ICH Q5E
Stakeholders
3Entities that collect blood and blood components and are the primary audience for this guidance.
Entities required to report implementation of DHQ documents
Entity providing information on software quality assurance for commercial packages.
Regulatory Context
Attributes
4blood group characteristic required for patient matching
Quantitative decision value for computer evaluation
Blood group classification required for determination.
Restriction on sample age for pretransfusion testing
Identified Hazards
Hazards
1Caused by clinically significant RBC antibodies
Related CFR Sections (10)
- 21CFR606.151§ 606.151 Compatibility testing.
Standard operating procedures for compatibility testing shall include the following:Read full regulation →
- 21CFR601.12§ 601.12 Changes to an approved application.
(a) General.Read full regulation →
- 21CFR640.120§ 640.120 Alternative procedures.
(a) The Director, Center for Biologics Evaluation and Research, may issue an exception or alternative to any requirement in subchapter F of chapter I of title 21 of the Code of Federal Regulations regarding blood, blood components, or blood products. The Director may issue such an exception or alterRead full regulation →
- 21CFR606.3§ 606.3 Definitions.
As used in this part:Read full regulation →
- 21CFR606.65§ 606.65 Supplies and reagents.
All supplies and reagents used in the collection, processing, compatibility testing, storage and distribution of blood and blood components shall be stored in a safe, sanitary and orderly manner.Read full regulation →
- 21CFR606.121§ 606.121 Container label.
(a) The container label requirements are designed to facilitate the use of a uniform container label for blood and blood components intended for use in transfusion or further manufacture by all blood establishments.Read full regulation →
- 21CFR606.100§ 606.100 Standard operating procedures.
(a) In all instances, except clinical investigations, standard operating procedures shall comply with published additional standards in part 640 of this chapter for the products being processed; except that, references in part 640 relating to licenses, licensed establishments and submission of materRead full regulation →
- 21CFR211.68§ 211.68 Automatic, mechanical, and electronic equipment.
(a) Automatic, mechanical, or electronic equipment or other types of equipment, including computers, or related systems that will perform a function satisfactorily, may be used in the manufacture, processing, packing, and holding of a drug product. If such equipment is so used, it shall be routinelyRead full regulation →
- 21CFR211.100§ 211.100 Written procedures; deviations.
(a) There shall be written procedures for production and process control designed to assure that the drug products have the identity, strength, quality, and purity they purport or are represented to possess. Such procedures shall include all requirements in this subpart. These written procedures, inRead full regulation →
- 21CFR606.160§ 606.160 Records.
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.
- 2025-12-11
CGMP/Finished Pharmaceuticals/Adulterated
Catalent Indiana, LLC
- 2025-12-09
CGMP/Finished Pharmaceuticals/Adulterated
DeVere Manufacturing Inc.
- 2025-12-09
CGMP/Finished Pharmaceuticals/Adulterated
CDL Services, Inc. DBA Technichem
- 2025-12-09
CGMP/Finished Pharmaceuticals/Adulterated
Seaway Pharma Inc.
- 2025-12-02
Compounding Pharmacy/Adulterated Drug Products
PQ Pharmacy, LLC
See Also (8)
- Alternative Tools: Assessing Drug Manufacturing Facilities Identified in Pending Applications (Status: Final)
- CPG Sec. 430.200 Repacking of Drug Products - Testing/Examination under CGMPs (Status: Final)
- CPG Sec. 425.300 Computerized Drug Processing; Source Code for Process Control Application Programs (Status: Final)
- CPG Sec. 410.100 *Finished Dosage Form Drug Products in Bulk Containers - Applications of Current Good Manufacturing Practice Regulations* (Status: Final)
- CPG Sec. 400.210, Radiofrequency Identification Feasibility Studies and Pilot Programs for Drugs (Status: Final)
- Reference Guide for the Nonclinical Toxicity Studies of Antivial Drugs Indicated for the Treatment of N/A Non-Life Threatening Disease Evaluation of Drug Toxicity Prior to Phase I Clinical Studies (Status: Final)
- Preparation of Investigational New Drug Products (Human and Animal): Guidance for Industry (Status: Final)
- Review of FDA's Implementation of the Drug Export Amendments of 1986 (Status: Final)