21 C.F.R. Subpart G—Finished Product Control
Title 21 - Food and Drugs
(a) Labeling operations shall be separated physically or spatially from other operations in a manner adequate to prevent mixups. (b) The labeling operation shall include the following labeling controls: (1) Labels shall be held upon receipt, pending review and proofing against an approved final copy, to ensure accuracy regarding identity, content, and conformity with the approved copy. (2) Each type of label representing different products shall be stored and maintained in a manner to prevent mixups, and stocks of obsolete labels shall be destroyed. (3) All necessary checks in labeling procedures shall be utilized to prevent errors in translating test results to container labels. (c) All labeling shall be clear and legible. [50 FR 35469, Aug. 30, 1985] (a) The container label requirements are designed to facilitate the use of a uniform container label for blood and blood components (except Source Plasma) by all blood establishments. (b) The label provided by the collecting facility and the initial processing facility shall not be removed, altered, or obscured, except that the label may be altered to indicate the proper name and other information required to identify accurately the contents of a container after blood components have been prepared. (c) The container label shall include the following information, as well as other specialized information as required in this section for specific products: (1) The proper name of the product in a prominent position, and modifier(s), if appropriate. (2) The name, address, registration number, and, if a licensed product, the license number of each manufacturer. (3) The donor, pool, or lot number relating the unit to the donor. (4) The expiration date, including the day, month, and year, and, if the dating period for the product is 72 hours or less, the hour of expiration. (5) If the product is intended for transfusion, the appropriate donor classification statement, i.e., “paid donor” or “volunteer donor”, in no less prominence than the proper name of the product. (i) A paid donor is a person who receives monetary payment for a blood donation. (ii) A volunteer donor is a person who does not receive monetary payment for a blood donation. (iii) Benefits, such as time off from work, membership in blood assurance programs, and cancellation of nonreplacement fees that are not readily convertible to cash, do not constitute monetary payment within the meaning of this paragraph. (6) For Whole Blood, Plasma, Platelets, and partial units of Red Blood Cells, the volume of the product, accurate to within ±10 percent; or optionally for Platelets, the volume range within reasonable limits. (7) The recommended storage temperature (in degrees Celsius). (8) If the product is intended for transfusion, the statements: (i) “Rx only.” (ii) “See circular of information for indications, contraindications, cautions, and methods of infusion.” (iii) “Properly identify intended recipient.” (9) The statement: “This product may transmit infectious agents.” (10) Where applicable, the name and volume of source material. (11) The statement: “Caution: For Manufacturing Use Only”, when applicable. (12) If the product is intended for transfusion, the ABO and Rh groups of the donor shall be designated conspicuously. For Cryoprecipitated AHF, the Rh group may be omitted. The Rh group shall be designated as follows: (i) If the test using Anti-D Blood Grouping Reagent is positive, the product shall be labeled: “Rh positive.” (ii) If the test using Anti-D Blood Grouping Reagent is negative but the test for Du is positive, the product shall be labeled: “Rh positive.” (iii) If the test using Anti-D Blood Grouping Reagent is negative and the test for Du is negative, the product shall be labeled: “Rh negative.” (13) The container label must bear encoded information in a format that is machine-readable and approved for use by the Director, Center for Biologics Evaluation and Research. (i) Who is subject to this machine-readable requirement? All blood establishments that manufacture, process, repack, or relabel blood or blood components intended for transfusion and regulated under the Federal Food, Drug, and Cosmetic Act or the Public Health Service Act. (ii) What blood products are subject to this machine-readable requirement? All blood and blood components intended for transfusion are subject to the machine-readable information label requirement in this section. (iii) What information must be machine-readable? Each label must have machine-readable information that contains, at a minimum: (A) A unique facility identifier; (B) Lot number relating to the donor; (C) Product code; and (D) ABO and Rh of the donor. (iv) How must the machine-readable information appear The machine-readable information must: (A) Be unique to the blood or blood component; (B) Be surrounded by sufficient blank space so that the machine-readable information can be scanned correctly; and (C) Remain intact under normal conditions of use. (v) Where does the machine-readable information go? The machine-readable information must appear on the label of any blood or blood component which is or can be transfused to a patient or from which the blood or blood component can be taken and transfused to a patient. (d) Except for recovered plasma intended for manufacturing use or as otherwise approved by the Director, Center for Biologics Evaluation and Research, the paper of the container label shall be white and print shall be solid black, with the following additional exceptions: (1) The Rh blood group shall be printed as follows: (i) Rh positive: Use black print on white background. (ii) Rh negative: Use white print on black background. (2) The proper name of the product, any appropriate modifier(s), the donor classification statement, and the statement “properly identify intended recipient” shall be printed in solid red or in solid black. (3) The following color scheme may be used optionally for differentiating ABO Blood groups: (4) Ink colors used for the optional color coding system described in paragraph (d)(3) of this section shall be a visual match to specific color samples designated by the Director, Center for Biologics Evaluation and Research. (5) Special labels, such as those described in paragraphs (h) and (i) of this section, may be color coded using the colors recommended in the guideline (see paragraph (a) of this section), or colors otherwise approved for use by the Director, Center for Biologics Evaluation and Research. (e) Container label requirements for particular products or groups of products. (1) Whole Blood labels shall include: (i) The volume of anticoagulant. (ii) The name of the applicable anticoagulant immediately preceding and of no less prominence than the proper name approved for use by the Director, Center for Biologics Evaluation and Research. (iii) If tests for unexpected antibodies are positive, blood intended for transfusion shall be labeled: “Contains (name of antibody).” (2) Except for frozen, deglycerolized, or washed Red Blood Cell products, red blood cell labels shall include: (i) The volume and kind of Whole Blood, including the type of anticoagulant, from which the product was prepared. (ii) If tests for unexpected antibodies are positive and the product is intended for transfusion, the statement: “Contains (name of antibody).” (3) Labels for products with a dating period of 72 hours or less, including any product prepared in a system that may compromise sterility, shall bear the hour of expiration. (4) If tests for unexpected antibodies are positive, Plasma intended for transfusion shall be labeled: “Contains (name of antibody).” (5) Recovered plasma labels shall include: (i) In lieu of an expiration date, the date of collection of the oldest material in the container. (ii) The statement as applicable: “Caution: For Manufacturing Use Only”; or “Caution: For Use in Manufacturing Noninjectable Products Only.” If the recovered plasma has a reactive screening test for evidence of infection due to a communicable disease agent(s) under §610.40 of this chapter, or is collected from a donor with a previous record of a reactive screening test for evidence of infection due to a communicable disease agent(s) under §610.40 of this chapter, the recovered plasma must be labeled as required under §610.40(h)(2)(ii)(E) of this chapter. (iii) For recovered plasma not meeting the requirements for manufacture into licensable products, the statement: “Not for Use in Products Subject to License Under Section 351 of the Public Health Service Act.” (f) Blood and blood components determined to be unsuitable for transfusion shall be prominently labeled: “NOT FOR TRANSFUSION”, and the label shall state the reason the unit is considered unsuitable. The provision does not apply to recovered plasma labeled according to paragraph (e)(5) of this section. (g) [Reserved] (h) The following additional information shall appear on the label for blood or blood components shipped in an emergency, prior to completion of required tests, in accordance with §640.2(f) of this chapter: (1) The statement: “FOR EMERGENCY USE ONLY BY ____.” (2) Results of any tests prescribed under §§610.40, and 640.5 (a), (b), or (c) of this chapter completed before shipment. (3) Indication of any tests prescribed under §§610.40, and 640.5 (a), (b), or (c) of this chapter and not completed before shipment. (i) The following additional information shall appear on the label for Whole Blood or Red Blood Cells intended for autologous infusion: (1) Information adequately identifying the patient, e.g., name, blood group, hospital, and identification number. (2) Date of donation. (3) The statement: “FOR AUTOLOGOUS USE ONLY.” (4) In place of the blood group label, each container of blood intended for autologous use and obtained from a donor who fails to meet any of the donor suitability requirements under §640.3 of this chapter or who is reactive in the hepatitis tests prescribed under §610.40 of this chapter shall be prominently and permanently labeled: “FOR AUTOLOGOUS USE ONLY.” (5) Units of blood originally intended for autologous use, except those labeled as prescribed under paragraph (i)(4) of this section, may be issued for homologous transfusion provided the container label complies with all applicable provisions of paragraphs (b) through (e) of this section. In such case, the special label required under paragraph (i) (1), (2), and (3) of this section shall be removed or otherwise obscured. (j) A tie-tag attached to the container may be used for providing the information required by paragraph (e) (1)(iii), (2)(ii), and (4), (h), or (i)(1), (2), and (3) of this section. [50 FR 35469, Aug. 30, 1985, as amended at 53 FR 116, Jan. 5, 1988; 55 FR 11014, Mar. 26, 1990; 57 FR 10814, Mar. 31, 1992; 59 FR 23636, May 6, 1994; 63 FR 16685, Apr. 6, 1998; 64 FR 45371, Aug. 19, 1999; 66 FR 31162, June 11, 2001; 67 FR 4907, Feb. 1, 2002; 69 FR 9171, Feb. 26, 2004; 70 FR 14984, Mar. 24, 2005] An instruction circular shall be available for distribution if the product is intended for transfusion. The instruction circular shall provide adequate directions for use, including the following information: (a) Instructions to mix the product before use. (b) Instructions to use a filter in the administration equipment. (c) The statement “Do Not Add Medications” or an explanation concerning allowable additives. (d) A description of the product, its source, and preparation, including the name and proportion of the anticoagulant used in collecting the Whole Blood from each product is prepared. (e) Statements that the product was prepared from blood that was negative when tested for antibody to Human Immunodeficiency Virus (HIV) and nonreactive for hepatitis B surface antigen by FDA required tests and nonreactive when tested for syphilis by a serologic test for syphilis (STS). (f) The statements: “Warning. The risk of transmitting infectious agents is present. Careful donor selection and available laboratory tests do not eliminate the hazard.” (g) The names of cryoprotective agents and other additives that may still be present in the product. (h) The names and results of all tests performed when necessary for safe and effective use. (i) The use of the product, indications, contradications, side effects and hazards, dosage and administration recommendations. (j) [Reserved] (k) For Red Blood Cells, the instruction circular shall contain: (1) Instructions to administer a suitable plasma volume expander if Red Blood Cells are substituted when Whole Blood is the indicated product. (2) A warning not to add Lactated Ringer's Injection U.S.P. solution to Red Blood Cell products. (l) For Platelets, the instruction circular shall contain: (1) The approximate volume of plasma from which a sample unit of Platelets is prepared. (2) Instructions to begin administration as soon as possible, but not more than 4 hours after entering the container. (m) For Plasma, the instruction circular shall contain: (1) A warning against further processing of the frozen product if there is evidence of breakage or thawing. (2) Instructions to thaw the frozen product at a temperature between 30 and 37 °C. (3) When applicable, instructions to begin administration of the product within 6 hours after thawing. (4) Instructions to administer to ABO-group-compatible recipients. (5) A statement that this product has the same hepatitis risk as Whole Blood; other plasma volume expanders without this risk are available for treating hypovolemia. (n) For Cryoprecipitated AHF, the instruction circular shall contain: (1) A statement that the average potency is 80 or more International Units of antihemophilic factor. (2) The statement: “Usually contains at least 150 milligrams of fibrinogen”; or, alternatively, the average fibrinogen level determined by assay of representative units. (3) A warning against further processing of the product if there is evidence of breakage or thawing. (4) Instructions to thaw the product for no more than 15 minutes at a temperature of between 30 and 37 °C. (5) Instructions to store at room temperature after thawing and to begin administration as soon as possible but no more than 4 hours after entering the container or after pooling and within 6 hours after thawing. (6) A statement that 0.9 percent Sodium Chloride Injection U.S.P. is the preferred diluent. (7) Adequate instructions for pooling to ensure complete removal of all concentrated material from each container. (8) The statement: “Good patient management requires monitoring treatment responses to Cryoprecipitated AHF transfusions with periodic plasma factor VIII or fibrinogen assays in hemophilia A and hypofibrinogenemic recipients, respectively.” [50 FR 35470, Aug. 30, 1985, as amended at 53 FR 116, Jan. 5, 1988; 64 FR 45371, Aug. 19, 1999]
Title 21: Food and Drugs
PART 606—CURRENT GOOD MANUFACTURING PRACTICE FOR BLOOD AND BLOOD COMPONENTS
Subpart G—Finished Product Control
§ 606.120 Labeling, general requirements.
§ 606.121 Container label.
------------------------------------------------------------------------ Blood group Color of label paper------------------------------------------------------------------------O BlueA YellowB PinkAB White------------------------------------------------------------------------
§ 606.122 Instruction circular.
