21 C.F.R. Subpart A—Whole Blood
Title 21 - Food and Drugs
The proper name of this product shall be Whole Blood. Whole Blood is defined as blood collected from human donors for transfusion to human recipients. [38 FR 32089, Nov. 20, 1973, as amended at 50 FR 4138, Jan. 29, 1985] (a) Manufacturing responsibility. All manufacturing of Whole Blood, including donor examination, blood collection, laboratory tests, labeling, storage and issue, shall be done under the supervision and control of the same licensed establishment except that the Director, Center for Biologics Evaluation and Research, may approve arrangements, upon joint request of two or more licensed establishments, which he finds are of such a nature as to assure compliance otherwise with the provisions of this subchapter. (b) Blood container. The blood container shall not be entered prior to issue for any purpose except for blood collection or when the method of processing requires use of a different container. The container shall be uncolored and transparent to permit visual inspection of the contents and any closure shall be such as will maintain a hermetic seal and prevent contamination of the contents. The container material shall not interact with the contents under the customary conditions of storage and use, in such a manner as to have an adverse effect upon the safety, purity, or potency of the blood. (c) Reissue of blood. Blood that has been removed from storage controlled by a licensed establishment shall not be reissued by a licensed establishment unless the following conditions are observed: (1) The container has a tamper-proof seal when originally issued and this seal remains unbroken; (2) A segment is properly attached and has not been removed, except that blood lacking a properly attached segment may be reissued in an emergency provided it is accompanied by instructions for sampling and for use within 6 hours after entering the container for sampling; (3) The blood has been stored continuously at 1 to 6 °C and shipped between 1 and 10 °C; (4) The blood is held for observation until a significant inspection consistent with the requirements of §640.5(e) can be made. [38 FR 32089, Nov. 20, 1973, as amended at 41 FR 4015, Jan. 28, 1976; 42 FR 59878, Nov. 22, 1977; 43 FR 34460, Aug. 4, 1978; 49 FR 15187, Apr. 18, 1984; 49 FR 23834, June 8, 1984; 50 FR 4138, Jan. 29, 1985; 53 FR 116, Jan. 5, 1988; 55 FR 11013, Mar. 26, 1990; 63 FR 16685, Apr. 6, 1998; 64 FR 45371, Aug. 19, 1999; 66 FR 1836, Jan. 10, 2001; 66 FR 31165, June 11, 2001; 66 FR 40889, Aug. 6, 2001; 67 FR 9587, Mar. 4, 2002] (a) Method of determining. The suitability of a donor as a source of Whole Blood shall be determined by a qualified physician or by persons under his supervision and trained in determining suitability. Such determination shall be made on the day of collection from the donor by means of medical history, a test for hemoglobin level, and such physical examination as appears necessary to a physician who shall be present on the premises when examinations are made, except that the suitability of donors may be determined when a physician is not present on the premises, provided the establishment (1) maintains on the premises, and files with the Center for Biologics Evaluation and Research, a manual of standard procedures and methods, approved by the Director of the Center for Biologics Evaluation and Research, that shall be followed by employees who determine suitability of donors, and (2) maintains records indicating the name and qualifications of the person immediately in charge of the employees who determine the suitability of donors when a physician is not present on the premises. (b) Qualifications of donor; general. Except as provided in paragraph (f) of this section and for autologous donations, a person may not serve as a source of Whole Blood more than once in 8 weeks. In addition, donors shall be in good health, as indicated in part by: (1) Normal temperature; (2) Demonstration that systolic and diastolic blood pressures are within normal limits, unless the examining physician is satisfied that an individual with blood pressures outside these limits is an otherwise qualified donor under the provisions of this section; (3) For allogeneic donors, a blood hemoglobin level which shall be demonstrated to be no less than 12.5 grams (g) of hemoglobin per 100 milliliters (mL) of blood; or a hematocrit value of 38 percent, and for autologous donors, a blood hemoglobin level which shall be demonstrated to be no less than 11.0 g of hemoglobin per 100 mL of blood or a hematocrit value of 33 percent. (4) Freedom from acute respiratory diseases; (5) Freedom from any infectious skin disease at the site of phlebotomy and from any such disease generalized to such an extent as to create a risk of contamination of the blood; (6) Freedom from any disease transmissible by blood transfusion, insofar as can be determined by history and examinations indicated above; and (7) Freedom of the arms and forearms from skin punctures or scars indicative of addiction to self-injected narcotics. (c) Additional qualifications of donor; viral hepatitis. No individual shall be used as a source of Whole Blood if he has— (1) A history of viral hepatitis after the 11th birthday; (2) A history of close contact within 12 months of donation with an individual having viral hepatitis; (3) A history of having received within 12 months of donation, human blood or any derivative of human blood which the Food and Drug Administration has advised the blood establishment is a possible source of viral hepatitis. (d) Therapeutic bleedings. Blood withdrawn in order to promote the health of a donor otherwise qualified under the provisions of this section, shall not be used as a source of Whole Blood unless the container label conspicuously indicates the donor's disease that necessitated withdrawal of blood. (e) [Reserved] (f) Qualifications; donations within less than 8 weeks. A person may serve as a source of Whole Blood more than once in 8 weeks only if at the time of donation the person is examined and certified by a physician to be in good health, as indicated in part in paragraph (b) of this section. [38 FR 32089, Nov. 20, 1973, as amended at 49 FR 23834, June 8, 1984; 50 FR 4138, Jan. 29, 1985; 51 FR 15611, Apr. 25, 1986; 55 FR 11013, Mar. 26, 1990; 64 FR 45371, Aug. 19, 1999; 66 FR 1836, Jan. 10, 2001; 66 FR 40889, Aug. 6, 2001] (a) Supervision. Blood shall be drawn from the donor by a qualified physician or under his supervision by assistants trained in the procedure. A physician shall be present on the premises when blood is being collected, except that blood may be collected when a physician is not present on the premises, provided the establishment (1) maintains on the premises, and files with the Center for Biologics Evaluation and Research, a manual of standard procedures and methods, approved by the Director of the Center for Biologics Evaluation and Research, that shall be followed by employees who collect blood, and (2) maintains records indicating the name and qualifications of the person immediately in charge of the employees who collect blood when a physician is not present on the premises. (b) The donor center. The pertinent requirements of §§600.10 and 600.11 of this chapter shall apply at both the blood establishment and at any other place where the bleeding is performed. (c) Blood containers. Blood containers and donor sets shall be pyrogen-free, sterile and identified by lot number. The amount of anticoagulant required for the quantity of blood to be collected shall be in the blood container when it is sterilized. In addition, all container and donor set surfaces that come in contact with blood used in the processing of Heparin Whole Blood shall be water repellent. (d) The anticoagulant solution. The anticoagulant solution shall be sterile and pyrogen-free. Anticoagulant solutions shall be compounded and used according to a formula approved by the Director, Center for Biologics Evaluation and Research. (e) Donor identification. Each unit of blood shall be so marked or identified by number or other symbol as to relate it to the individual donor whose identity shall be established to the extent necessary for compliance with §640.3. (f) Prevention of contamination of the blood. The skin of the donor at the site of phlebotomy shall be prepared thoroughly and carefully by a method that gives maximum assurance of a sterile container of blood. The blood shall be collected by aseptic methods in a sterile system which may be closed or may be vented if the vent protects the blood against contamination. (g) Samples and segments for laboratory tests. Samples and segments for laboratory tests shall meet the following standards: (1) One or more segments shall be provided with each unit of blood when issued or reissued except as provided in § 640.2(c)(2) and all segments shall be from the donor who is the source of the unit of blood. (2) All samples for laboratory tests performed by the manufacturer and all segments accompanying a unit of blood shall be collected at the time of filling the original blood container. (3) All containers for all samples shall bear the donor's identification before collecting the samples. (4) All segments accompanying a unit of blood shall be attached to the whole blood container before blood collection, in a tamperproof manner that will conspicuously indicate removal and reattachment. (5) Segments for compatibility testing shall contain blood mixed with the appropriate anticoagulant. (h) Storage. Immediately after collection, unless the blood is to be used as a source for Platelets, it shall be placed in storage at a temperature between 1 and 6 °C unless it must be transported from the donor clinic to the processing laboratory. In the latter case, the blood shall be placed in temporary storage having sufficient refrigeration capacity to cool the blood continuously toward a range between 1 and 6 °C until it arrives at the processing laboratory, where it shall be stored at a temperature between 1 and 6 °C. Blood from which Platelets is to be prepared shall be held in an environment maintained at a temperature range 20 to 24 °C until the platelets are separated. The red blood cells shall be placed in storage at a temperature between 1 and 6 °C immediately after the platelets are separated. [38 FR 32089, Nov. 20, 1973, as amended at 42 FR 59878, Nov. 22, 1977; 43 FR 34460, Aug. 4, 1978; 49 FR 23834, June 8, 1984; 50 FR 4138, Jan. 29, 1985; 55 FR 11013, Mar. 26, 1990; 64 FR 45372, Aug. 19, 1999; 66 FR 1836, Jan. 10, 2001; 66 FR 40889, Aug. 6, 2001] All laboratory tests shall be made on a specimen of blood taken from the donor at the time of collecting the unit of blood, and these tests shall include the following: (a) Serological test for syphilis. Whole Blood shall be negative to a serological test for syphilis. (b) Determination of blood group. Each container of Whole Blood shall be classified as to ABO blood group. At least two blood group tests shall be made and the unit shall not be issued until grouping tests by different methods or with different lots of antiserums are in agreement. Only those Anti-A and Anti-B Blood Grouping Reagents licensed under, or that otherwise meet the requirements of, the regulations of this subchapter shall be used, and the technique used shall be that for which the serum is specifically designed to be effective. (c) Determination of the Rh factors. Each container of Whole Blood shall be classified as to Rh type on the basis of tests done on the sample. The label shall indicate the extent of typing and the results of all tests performed. If the test, using Anti-D Blood Grouping Reagent, is positive, the container may be labeled “Rh Positive.” If the test is negative, the results shall be confirmed by further testing which shall include tests for the “weak D (formerly Du ).” Blood may be labeled “Rh Negative” if further testing is negative. Units testing positive after additional more specific testing shall be labeled as “Rh Positive.” Only Anti-Rh Blood Grouping Reagents licensed under, or that otherwise meet the requirements of, this subchapter shall be used, and the technique used shall be that for which the reagent is specifically designed to be effective. (d) Sterility test. Whole Blood intended for transfusion shall not be tested for sterility by a method that entails entering the final container before the blood is used for transfusion. (e) Inspection. Whole Blood shall be inspected visually during storage and immediately prior to issue. If the color or physical appearance is abnormal or there is any indication or suspicion of microbial contamination the unit of Whole Blood shall not be issued for transfusion. (f) Test for communicable disease agents. Whole Blood shall be tested for evidence of infection due to communicable disease agents as required under §610.40 of this chapter. [38 FR 32089, Nov. 20, 1973, as amended at 50 FR 4138, Jan. 29, 1985; 53 FR 117, Jan. 5, 1988; 53 FR 12764, Apr. 19, 1988; 64 FR 45372, Aug. 19, 1999; 66 FR 1836, Jan. 10, 2001; 66 FR 31165, June 11, 2001; 66 FR 40889, Aug. 6, 2001] Upon approval by the Director, Center for Biologics Evaluation and Research, of a supplement to the biologics license application for Whole Blood a manufacturer may prepare Whole Blood from which the antihemophilic factor has been removed, provided the Whole Blood meets the applicable requirements of this subchapter and the following conditions are met: (a) The antihemophilic factor shall be removed in accordance with paragraphs (a), (b), and (c) of §640.52. (b) Although the closed system between the red blood cells and plasma shall be maintained, the red blood cells shall be maintained between 1 and 6° C at all times, including that time when the plasma is being frozen for removal of the antihemophilic factor. [38 FR 32089, Nov. 20, 1973, as amended at 49 FR 23834, June 8, 1984; 50 FR 4138, Jan. 29, 1985; 55 FR 11013, Mar. 26, 1990; 59 FR 49351, Sept. 28, 1994; 64 FR 45372, Aug. 19, 1999; 64 FR 56453, Oct. 20, 1999]
Title 21: Food and Drugs
PART 640—ADDITIONAL STANDARDS FOR HUMAN BLOOD AND BLOOD PRODUCTS
Subpart A—Whole Blood
§ 640.1 Whole Blood.
§ 640.2 General requirements.
§ 640.3 Suitability of donor.
§ 640.4 Collection of the blood.
§ 640.5 Testing the blood.
§ 640.6 Modifications of Whole Blood.
