21 C.F.R. Subpart F—Production and Process Controls
Title 21 - Food and Drugs
(a) In all instances, except clinical investigations, standard operating procedures shall comply with published additional standards in part 640 of this chapter for the products being processed; except that, references in part 640 relating to licenses, licensed establishments and submission of material or data to or approval by the Director, Center for Biologics Evaluation and Research, are not applicable to establishments not subject to licensure under section 351 of the Public Health Service Act. (b) Written standard operating procedures shall be maintained and shall include all steps to be followed in the collection, processing, compatibility testing, storage, and distribution of blood and blood components for transfusion and further manufacturing purposes. Such procedures shall be available to the personnel for use in the areas where the procedures are performed. The written standard operating procedures shall include, but are not limited to, descriptions of the following, when applicable: (1) Criteria used to determine donor suitability, including acceptable medical history criteria. (2) Methods of performing donor qualifying tests and measurements, including minimum and maximum values for a test or procedure when a factor in determining acceptability. (3) Solutions and methods used to prepare the site of phlebotomy to give maximum assurance of a sterile container of blood. (4) Method of accurately relating the product(s) to the donor. (5) Blood collection procedure, including in-process precautions taken to measure accurately the quantity of blood removed from the donor. (6) Methods of component preparation, including any time restrictions for specific steps in processing. (7) All tests and repeat tests performed on blood and blood components during manufacturing. (8) Pretransfusion testing, where applicable, including precautions to be taken to identify accurately the recipient blood samples and crossmatched donor units. (9) Procedures for investigating adverse donor and recipient reactions. (10) Storage temperatures and methods of controlling storage temperatures for all blood products and reagents as prescribed in §§600.15 and 610.53 of this chapter. (11) Length of expiration dates, if any, assigned for all final products as prescribed in §610.53 of this chapter. (12) Criteria for determining whether returned blood is suitable for reissue. (13) Procedures used for relating a unit of blood or blood component from the donor to its final disposition. (14) Quality control procedures for supplies and reagents employed in blood collection, processing and pretransfusion testing. (15) Schedules and procedures for equipment maintenance and calibration. (16) Labeling procedures, including safeguards to avoid labeling mixups. (17) Procedures of plasmapheresis, plateletpheresis, and leukapheresis, if performed, including precautions to be taken to ensure reinfusion of a donor's own cells. (18) Procedures for preparing recovered plasma, if performed, including details of separation, pooling, labeling, storage, and distribution. (19) Procedures in accordance with §610.46 of this chapter to look at prior donations of Whole Blood, blood components, Source Plasma and Source Leukocytes from a donor who has donated blood and subsequently tests repeatedly reactive for antibody to human immunodeficiency virus (HIV) or otherwise is determined to be unsuitable when tested in accordance with §610.45 of this chapter. Procedures to quarantine in-house Whole Blood, blood components, Source Plasma and Source Leukocytes intended for further manufacture into injectable products that were obtained from such donors; procedures to notify consignees regarding the need to quarantine such products; procedures to determine the suitability for release of such products from quarantine; procedures to notify consignees of Whole Blood, blood components, Source Plasma and Source Leukocytes from such donors of the results of the antibody testing of such donors; and procedures in accordance with §610.47 of this chapter to notify attending physicians so that transfusion recipients are informed that they may have received Whole Blood and, blood components at increased risk for transmitting human immunodeficiency virus. (20) Procedures for donor deferral as prescribed in §610.41 of this chapter; and procedures for donor notification and autologous donor referring physician notification, including procedures for the appropriate followup if the initial attempt at notification fails, as prescribed in §630.6 of this chapter. (c) All records pertinent to the lot or unit maintained pursuant to these regulations shall be reviewed before the release or distribution of a lot or unit of final product. The review or portions of the review may be performed at appropriate periods during or after blood collecting, processing, compatibility testing and storing. A thorough investigation, including the conclusions and followup, of any unexplained discrepancy or the failure of a lot or unit to meet any of its specifications shall be made and recorded. (d) In addition to the requirements of this subpart and in conformity with this section, any facility may utilize current standard operating procedures such as the manuals of the organizations, as long as such specific procedures are consistent with, and at least as stringent as, the requirements contained in this part. (1) American Association of Blood Banks. (2) American National Red Cross. (3) Other organizations or individual blood banks, subject to approval by the Director, Center for Biologics Evaluation and Research. [40 FR 53532, Nov. 18, 1975, as amended at 49 FR 23833, June 8, 1984; 55 FR 11013, Mar. 26, 1990; 61 FR 47422, Sept. 9, 1996; 64 FR 45370, Aug. 19, 1999; 66 FR 31176, June 11, 2001] (a) The use of plateletpheresis and leukapheresis procedures to obtain a product for a specific recipient may be at variance with the additional standards for specific products prescribed in this part provided that: (1) A physician has determined that the recipient must be transfused with the leukocytes or platelets from a specific donor, and (2) the procedure is performed under the supervision of a qualified licensed physician who is aware of the health status of the donor, and the physician has certified in writing that the donor's health permits plateletpheresis or leukapheresis. (b) Plasmapheresis of donors who do not meet the donor requirements of §§640.63, 640.64 and 640.65 of this chapter for the collection of plasma containing rare antibodies shall be permitted only with the prior approval of the Director, Center for Biologics Evaluation and Research. [40 FR 53532, Nov. 18, 1975, as amended at 49 FR 23833, June 8, 1984; 55 FR 11013, Mar. 26, 1990]
Title 21: Food and Drugs
PART 606—CURRENT GOOD MANUFACTURING PRACTICE FOR BLOOD AND BLOOD COMPONENTS
Subpart F—Production and Process Controls
§ 606.100 Standard operating procedures.
§ 606.110 Plateletpheresis, leukapheresis, and plasmapheresis.
