FDA, AABB Requirements

This section covers the crucial regulatory and accreditation framework that governs how blood is processed in the lab. Think of the FDA (Food and Drug Administration) and AABB (Association for the Advancement of Blood & Biotherapies) as the two main pillars ensuring the safety, purity, and potency of blood products. They work together, but have distinct roles:

• FDA: The US government’s regulatory agency. Their requirements, primarily found in the Code of Federal Regulations (CFR) Title 21, Parts 600-680 (specifically 606 for GMPs, 610 for testing, 640 for product standards), are the law. Compliance is mandatory for any facility collecting or processing blood. They focus on setting minimum standards for safety and efficacy
• AABB: An international, non-profit accrediting organization. They publish Standards for Blood Banks and Transfusion Services. These standards often incorporate and sometimes exceed FDA requirements, representing industry best practices. While AABB accreditation is technically voluntary, it’s widely recognized as the hallmark of quality and is often required for hospital operations and reimbursement

Both FDA regulations and AABB standards aim to ensure every unit of blood is safe for transfusion. Here’s a breakdown of key requirements during the processing phase (after collection, before storage/distribution):

Overarching Requirements (Apply throughout Processing)

• Quality Management System (QMS)
  • FDA (Current Good Manufacturing Practices - cGMPs - 21 CFR 606): Mandates comprehensive quality systems covering personnel, facilities, equipment, procedures, records, error management, etc
  • AABB (Quality System Essentials - QSEs): Provides a detailed framework for quality management, often used as a model for implementing cGMPs. Covers areas like process control, documents & records, assessments, non-conformance management, and personnel training
  • Key Idea: Have robust systems in place to ensure quality is built into every step, not just tested at the end
• Personnel & Training
  • FDA & AABB: Require an adequate number of qualified personnel with defined responsibilities. Staff must receive initial and ongoing training relevant to their tasks. Competency must be assessed and documented regularly
• Facilities & Equipment
  • FDA & AABB: Facilities must be clean, orderly, and of suitable size and construction. Critical equipment (centrifuges, refrigerators, freezers, irradiators, sterile connection devices, testing instruments) must be qualified, calibrated, maintained, and monitored according to established schedules. Procedures must be in place for equipment malfunction
• Standard Operating Procedures (SOPs)
  • FDA & AABB: Written, detailed procedures must exist for all significant steps in processing. These SOPs must be readily available, followed precisely by staff, and reviewed/updated regularly. Any deviations must be documented
• Record Keeping & Traceability
  • FDA & AABB: Meticulous records are essential! Must allow tracking of a unit from the donor through all processing steps to its final disposition (transfusion, shipment, or discard) – often called “vein-to-vein” traceability. Records must be legible, accurate, contemporaneous, and retained for specified periods (often 10+ years). Computer systems used must be validated

Specific Processing Step Requirements

• Component Preparation
  • FDA & AABB: Procedures for separating whole blood into components (RBCs, Plasma, Platelets, Cryoprecipitate) must be validated to consistently produce products meeting specific quality criteria (e.g., volume, cell count, residual plasma/RBCs). Centrifugation speeds, times, and temperatures are critical parameters. Maintaining a closed system whenever possible is crucial to prevent contamination
• Testing (Donor Units)
  • FDA (21 CFR 610): Mandates testing of every donation using FDA-licensed test kits for specific transfusion-transmitted infections (TTIs). Current required tests include:
    • HIV-1/2 (antibody and NAT - Nucleic Acid Testing)
    • Hepatitis C (HCV) (antibody and NAT)
    • Hepatitis B (HBV) (HBsAg, anti-HBc, and NAT)
    • HTLV-I/II (Human T-lymphotropic virus) (antibody)
    • Syphilis (serological test)
    • West Nile Virus (WNV) (NAT)
    • Zika Virus (NAT - under specific guidance)
    • Trypanosoma cruzi (Chagas disease) (antibody - usually once per donor)
    • Babesia microti (NAT or antibody - required in certain states, recommended elsewhere)
  • AABB: Standards align with FDA requirements for TTI testing. May have additional recommendations or requirements based on emerging risks
  • Immunohematology Testing
    • FDA & AABB: ABO group and Rh type (including weak D testing based on policy) are required for all donations. Antibody screen required for donors with a history of transfusion or pregnancy. Results must be compared with historical records if available
• Labeling
  • FDA (21 CFR 606 Subpart G): Specifies mandatory information for container labels. Labels must be accurate, clear, and indelible. A system must be in place to prevent labeling errors
  • AABB: Strongly advocates for and requires the use of the ISBT 128 international labeling standard for uniformity and enhanced safety (barcodes, standardized product codes, ABO/Rh representation)
  • Critical Step: Final component labels confirming suitability (e.g., ABO/Rh, expiration date, negative infectious disease results) can only be applied after all required testing is completed, reviewed, and found acceptable. Units must remain in quarantine until this final labeling occurs
  • Label Content: Includes unique donation ID, component name, ABO/Rh, volume, anticoagulant/additive, storage temp, expiration date/time, facility info, donor status (volunteer/autologous), and any special attributes (Irradiated, Leukoreduced, CMV Seronegative, Antigen Negative, etc.)
• Modifications (Leukoreduction, Irradiation, Washing, etc.)
  • FDA & AABB: If components are modified, the process must be validated, performed according to SOPs, and documented
    • Leukoreduction: Must meet specific standards for residual white blood cell count (e.g., < 5 x 10⁶ WBCs per unit in the US). QC testing is required
    • Irradiation: Requires a validated process delivering a specific dose range (typically 25-50 Gy) to prevent TA-GVHD. An irradiation indicator label is usually applied
    • Washing/Volume Reducing: Procedures must minimize residual plasma or additive solution while maintaining component quality. Affects expiration time
    • Freezing/Deglycerolizing (RBCs): Requires specific glycerolization, freezing, thawing, and deglycerolization protocols. Post-thaw/deglycerolization expiration is short (usually 24 hours if an open system)
• Quarantine & Release
  • FDA & AABB: Units must be held in a designated quarantine area until all mandatory testing, component preparation, and record review are complete and acceptable. Only then can units be labeled appropriately and released to inventory for storage or distribution. Procedures must prevent the inadvertent release of unsuitable units

Key Takeaway

Both FDA regulations (the law) and AABB standards (best practices/accreditation) provide a comprehensive framework for blood processing. Adherence isn’t optional; it’s fundamental to ensuring that every blood component prepared in the lab is safe, pure, potent, and correctly labeled before it ever reaches a patient. This requires meticulous attention to detail, robust quality systems, and well-trained staff following validated procedures

Key Terms

• FDA (Food and Drug Administration): The US federal agency responsible for regulating blood products as biological drugs
• AABB (Association for the Advancement of Blood & Biotherapies): Professional organization setting standards and providing accreditation for blood banks and transfusion services
• CFR (Code of Federal Regulations): Where FDA regulations are published (Title 21 for Food and Drugs)
• cGMP (Current Good Manufacturing Practices): FDA regulations (21 CFR 606) outlining the minimum requirements for methods, facilities, and controls used in manufacturing (including blood collection/processing)
• AABB Standards: The detailed requirements published by AABB for accredited facilities
• ISBT 128: An international standard for the terminology, coding, and labeling of medical products of human origin (blood, cells, tissues). Uses standardized barcodes and product codes
• Quality Management System (QMS): The organizational structure, procedures, processes, and resources needed to implement quality management
• Validation: Documented evidence providing a high degree of assurance that a specific process will consistently produce a product meeting predetermined specifications and quality attributes
• Traceability: The ability to track a blood unit from the donor source through all steps of processing and testing to its final disposition (including the recipient)
• Leukoreduction: The process of removing white blood cells (leukocytes) from a blood component
• Irradiation: Treating blood components with gamma rays or X-rays to inactivate T-lymphocytes and prevent Transfusion-Associated Graft-versus-Host Disease (TA-GVHD)
• NAT (Nucleic Acid Testing): Highly sensitive molecular tests that detect the genetic material (RNA or DNA) of viruses, allowing for earlier detection of infections compared to antibody tests