21 CFR 606Current Good Manufacturing Practice for Blood and Blood Components
Part 606 is the FDA cGMP rulebook for blood centers and transfusion services. It defines personnel, facility, equipment, supply, production, records, and labelling requirements for whole blood, components, and source plasma — the regulator's expectation of how a unit moves from donor arm to recipient vein without compromising safety, purity, or potency.
01What Part 606 covers
21 CFR Part 606 is the cGMP regulation specific to blood and blood components for transfusion. It applies to every establishment that collects, prepares, processes, tests, labels, stores, or distributes whole blood, packed red blood cells, platelets, plasma, cryoprecipitate, granulocytes, or source plasma. It's the Part 211 of the blood world — but rewritten for a perishable biologic with a donor as the starting material instead of an API.
Part 606 doesn't stand alone. A blood center is also subject to Part 600 (biologics establishment standards), Part 610 (general biological product standards — including the lookback rules), Part 630 (donor eligibility for blood), Part 640 (additional standards for specific blood products), and Part 11 (electronic records and signatures). And if the establishment ships across state lines or holds a biologics licence, FDA Form 356h and the BLA file the licence is built on impose additional product-specific obligations.
02Structure — what each subpart imposes
| Subpart | Topic |
|---|---|
| A — 606.3 | Definitions (unit, component, donor, processing, etc.). |
| B — 606.20–606.40 | Personnel, plant, and equipment requirements. |
| C — 606.60–606.65 | Equipment maintenance, calibration, supplies, reagents. |
| D — 606.100–606.122 | Production and process controls; SOPs; container labels; circular of information. |
| E — 606.140–606.171 | Laboratory controls — testing of donations and components. |
| F — 606.160–606.171 | Records (retention, content, transfer) and reports (fatalities, biological product deviations). |
03Production and process controls — Subpart D in practice
Section 606.100 requires written standard operating procedures for every step of collection, preparation, testing, storage, and distribution. The SOPs must be available where the work happens, must be followed as written, and any deviation must be recorded and investigated. The list of mandatory SOPs in 606.100(b) is long — donor selection, collection, anticoagulant ratio, component preparation, testing, labelling, storage, shipping, recall, etc. — and an inspector will read your SOP index against this list line by line.
Component labelling is one of the most cited areas in Form 483s and warning letters. 606.121 specifies what must appear on the container (proper name, donation identification number, ABO group and Rh type, expiration date, storage temperature, name and address of the collecting establishment, volume or weight, anticoagulant). 606.122 specifies what must appear in the Circular of Information that accompanies every shipment. Most US blood centres meet these requirements using ISBT 128 product codes and labels, but ISBT 128 is the implementation — Part 606 is the rule.
04Laboratory controls and infectious-disease testing
Subpart E requires testing for ABO group, Rh factor, and infectious disease markers on every donation. The IDM panel is defined in 21 CFR 610.40 and supplemented by FDA guidance: HIV-1/2 (antibody + NAT), HBV (HBsAg + anti-HBc + NAT), HCV (antibody + NAT), HTLV-I/II (antibody, first-time donors), syphilis, West Nile virus (NAT, in qualifying months), Zika virus (per current FDA guidance), Trypanosoma cruzi (antibody, first-time donors). Bacterial detection on platelets is required under 21 CFR 606.145.
Tests must be performed using FDA-licensed, approved, or cleared assays in a laboratory that meets CLIA or equivalent. A unit cannot be released for transfusion until all required tests are complete and non-reactive. Reactive results trigger donor deferral, lookback, and notification under 610.46/47.
05Records and reports — Subpart F
Records must be retained for at least 10 years after the records of processing are completed or the expiration of the component, whichever is later. Records that relate to donor deferral, look-back, or notification have no expiration — they must be kept indefinitely. Records must be legible, accessible, secure, and made available to FDA on request. Electronic records must meet 21 CFR Part 11.
Two reports are mandatory and time-bound. Fatal donation- or transfusion-related fatalities must be reported to CBER as soon as possible (preliminary notification within 24 hours of becoming aware, written report within 7 days) under 606.170(b). Biological product deviations — any event associated with manufacturing in which the safety, purity, or potency of a distributed product may be affected — must be reported on Form FDA 3486 within 45 days under 606.171.
Frequently asked questions
Q.How does Part 606 differ from 21 CFR 211?+
Part 606 is purpose-built for blood: it talks about donors, components, anticoagulant, and ISBT-128-style labelling instead of APIs and tablet weights. The underlying philosophy is identical — written SOPs, trained people, qualified equipment, signed records, immutable retention — but the regulator-facing vocabulary is different.
Q.Does a hospital transfusion service have to register under Part 606?+
If the service only stores, tests for compatibility, and issues blood for transfusion, it's regulated under Part 606 by reference but does not need a biologics license. A facility that collects, processes, or labels components for transfusion does need to register and may need a BLA.
Q.Is bacterial detection on platelets required?+
Yes — 21 CFR 606.145, finalised in 2020, requires methods to detect or limit the risk of bacterial contamination of all platelet components. The acceptable strategies are spelled out in FDA's 2020 guidance: large-volume delayed sampling culture, secondary culture, or pathogen reduction.
Q.What about apheresis platelets vs whole-blood-derived platelets?+
Both are covered by Part 606. Component-specific standards live in 21 CFR 640 — Subpart D for platelets, Subpart E for cryoprecipitate, etc. Apheresis donor management is also subject to 21 CFR 640.20–640.27.
Q.Where does AABB fit in?+
AABB Standards are voluntary accreditation that goes beyond Part 606 in many areas. AABB-accredited centres are still inspected by FDA against Part 606 — accreditation is in addition to, not in place of, the regulation.
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