3.1 Processing: FDA/AABB Requirements, Testing, and Labeling

Processing is the manufacturing interval between collection and labeled release. For BB(ASCP), treat every donation as a licensed biologic. 21 CFR 606 sets current good manufacturing practice for blood establishments. 21 CFR 610 governs required tests and restrictions on shipment or use. 21 CFR 630 covers donor eligibility. 21 CFR 640 adds component-specific manufacturing rules for Whole Blood, Red Blood Cells, Platelets, Plasma, and Cryoprecipitated AHF. AABB Standards for Blood Banks and Transfusion Services (35th edition, effective 1 April 2026) implement those federal rules inside an accredited quality system. A unit is not finished when the bag is full. It is finished when required tests are complete, quarantine holds are cleared, and the ISBT-128 label matches the donor, the product, and the test file.

Manufacturing sequence and quarantine

After whole-blood or apheresis collection, the establishment prepares components in a closed sterile system, keeps the original donor identification on every satellite bag and integral segment, and places products in quarantine. Quarantine is a controlled status, not a refrigerator shelf. The computer and the physical inventory both treat the unit as unavailable for routine allogeneic issue until ABO/Rh (including weak D when the donor types D-negative), the unexpected-antibody screen, and the current FDA infectious-disease panel are complete and acceptable. Computer release compares the donation identification number (DIN) to the test results. A missing, pending, or reactive result blocks issue.

21 CFR 610.40(g) allows release or shipment before testing only in a documented medical emergency, or for further manufacturing as approved in writing by FDA. Even then the consignee must receive required labeling and prompt results. That exception is not a workaround for a thin Friday inventory. Do not release untested allogeneic units into ordinary stock.

Autologous collections follow a different label path. If the unit will never be crossed over, FDA does not require the full allogeneic infectious-disease panel on every donation; untested autologous units are labeled DONOR UNTESTED. If any autologous unit may be used for allogeneic transfusion, the establishment must test all autologous donations under 21 CFR 610.40. A reactive autologous unit that is still issued to the donor carries a BIOHAZARD legend. Crossover of an untested or reactive autologous unit into allogeneic inventory is not permitted.

ABO, Rh, and the donor weak-D rule

21 CFR 640.5 requires ABO grouping by at least two methods or two reagent lots that agree before issue. Rh typing uses licensed Anti-D. If the donor is immediately D-negative, the establishment must perform further testing that includes weak D (formerly D^u). A donor who is weak-D positive is labeled Rh positive. This is the opposite of the usual recipient rule: a patient who types D-negative is typically treated as D-negative and given D-negative red cells, because a partial-D recipient can make anti-D. Mixing those two policies is a high-yield BB trap.

AABB requires an unexpected-antibody screen on allogeneic donations. A donor with anti-K or another alloantibody can still supply packed red cells after most of the plasma is removed, but plasma, platelets, and cryoprecipitate from that donation are not issued as ordinary plasma-containing products. The computer record and, when required, the label must carry the antibody information so a downstream transfusion service does not infuse incompatible plasma.

Current FDA infectious-disease markers (2026)

21 CFR 610.40 requires testing of each allogeneic donation for relevant transfusion-transmitted infections (RTTIs) using licensed donor-screening tests, unless FDA has accepted an alternative such as one-time testing, regional testing, or pathogen reduction. As of 2026 the operational U.S. allogeneic panel is:

Zika virus was an RTTI with nationwide NAT after 2016. In May 2021 FDA determined Zika no longer has sufficient incidence or prevalence to remain an RTTI and withdrew the testing guidance. Licensed establishments that discontinued Zika NAT report that change. Do not list Zika as a current required marker on a 2026 exam item unless the question is historical.

Babesia remains current. FDA guidance treats transfusion-transmitted babesiosis as a relevant risk in endemic regions and recommends year-round licensed Babesia NAT, or an FDA-approved pathogen-reduction device, for donations collected in Connecticut, Delaware, Maine, Maryland, Massachusetts, Minnesota, New Hampshire, New Jersey, New York, Pennsylvania, Rhode Island, Vermont, Virginia, Wisconsin, and Washington, D.C. Outside those regions, establishments that do not pathogen-reduce must still ask about a history of babesiosis or a prior positive Babesia test. A reactive result interdicts the donation.

Platelets stored at 20–24 °C require a bacterial-risk-control strategy in addition to the viral and parasitic panel. Acceptable approaches under FDA guidance include pathogen reduction and culture-based methods such as large-volume delayed sampling. Depending on the approved strategy, dating is 5 days or, with an approved 7-day strategy and container, 7 days. Bacterial detection is a processing and release requirement, not an optional add-on.

A reactive screening test triggers supplemental or confirmatory testing when a licensed supplemental test exists (21 CFR 610.40(e)), donor notification and deferral, and interdiction of the current donation. A first-time donor who feels well is not “probably fine” if a marker is repeatedly reactive.

Lookback and recipient notification

Lookback starts when a donor later tests reactive or confirmed-positive, or is implicated in a transfusion-transmitted infection. The collecting establishment quarantines remaining in-date components from that donor and notifies consignees of prior collections inside the FDA lookback window. HIV lookback is 21 CFR 610.46; HCV lookback is 21 CFR 610.47. Analogous retrieval and notification apply to other markers under FDA guidance and AABB Standards. The transfusion service then notifies the recipient’s physician so the recipient can be offered testing and counseling. Destroying only the current reactive unit and hoping prior units were already transfused is not compliance.

ISBT-128 labeling

ISBT-128 replaced Codabar so every unit carries globally unique, machine-readable identifiers. The exam expects the data groups, not the barcode symbology:

• DIN — unique donation identification number tying every component and segment to one collection event.
• Product code — component class plus modifiers (leukoreduced, washed, frozen, apheresis, pooled).
• ABO/Rh — eye-readable and barcoded; must match the two-method type, including donor weak-D status.
• Expiration — date, and time when dating is measured in hours.
• Facility identifiers — FDA-registered collection facility and, if different, the processing or labeling facility.
• Anticoagulant or additive and volume.
• Special testing — CMV serostatus, hemoglobin S-negative, antigen-negative phenotype. These are not required on every allogeneic unit; they appear when the test was performed and the attribute is claimed.
• Irradiation indicator when the unit has received a validated irradiating dose.
• Volunteer versus paid donor statement and the infectious-agent warning required by 21 CFR 606.121.

A unit missing a required element is not issued. Relabeling after modification (irradiation, washing, pooling, thawing) must update the product code and the new expiration. If the DIN, ABO/Rh, or expiration on the bag disagrees with the test file, stop. Do not “fix” a mismatch by handwriting over a barcode.

Worked scenario. A D-negative first-time donor collected in Massachusetts has nonreactive viral markers, a negative antibody screen, pending Babesia NAT, and a weak-D test that is positive. The red-cell bag cannot be released while Babesia NAT is pending. When that result is nonreactive, the unit is labeled Rh positive, not Rh-negative. Releasing it as D-negative because the immediate-spin Anti-D was negative is a labeling error.

Exam traps. Do not release untested allogeneic units. Do not treat a weak-D-positive donor as Rh-negative. Do not still require Zika NAT. Do not apply Babesia NAT as a nationwide every-donation rule; it is endemic-region NAT or pathogen reduction. Do not skip bacterial-risk control on room-temperature platelets. Do not issue a unit whose ISBT-128 ABO/Rh, DIN, or expiration disagrees with the test file.