Food and Drug Administration, HHS § 606.3
all studies and tests of a biological Subpart A—General Provisions product on animals and humans and all studies and tests on the drug for iden- § 606.3 Definitions. tity, stability, purity, potency, and As used in this part: bioavailability. (a) Blood means whole blood collected [39 FR 44656, Dec. 24, 1974, as amended at 42 from a single donor and processed ei- FR 15676, Mar. 22, 1977; 49 FR 23833, June 8, ther for transfusion or further manu- 1984; 55 FR 11013, Mar. 26, 1990; 61 FR 51530, facturing. Oct. 2, 1996] (b) Unit means the volume of blood or one of its components in a suitable vol- PART 606—CURRENT GOOD MAN- ume of anticoagulant obtained from a UFACTURING PRACTICE FOR single collection of blood from one BLOOD AND BLOOD COMPO- donor. NENTS (c) Component means that part of a single-donor unit of blood separated by Subpart A—General Provisions physical or mechanical means. Sec. (d) Plasma for further manufacturing 606.3 Definitions. means that liquid portion of blood sep- arated and used as material to prepare Subpart B—Organization and Personnel another product. (e) Plasmapheresis means the proce- 606.20 Personnel. dure in which blood is removed from Subpart C—Plant and Facilities the donor, the plasma is separated from the formed elements and at least 606.40 Facilities. the red blood cells are returned to the donor. This process may be imme- Subpart D—Equipment diately repeated, once. 606.60 Equipment. (f) Plateletpheresis means the proce- 606.65 Supplies and reagents. dure in which blood is removed from the donor, a platelet concentrate is Subpart E [Reserved] separated, and the remaining formed elements and residual plasma are re- Subpart F—Production and Process turned to the donor. Controls (g) Leukapheresis means the proce- 606.100 Standard operating procedures. dure in which blood is removed from 606.110 Plateletpheresis, leukapheresis, and the donor, a leukocyte concentrate is plasmapheresis. separated, and the remaining formed elements and residual plasma are re- Subpart G—Finished Product Control turned to the donor. (h) Facilities means any area used for 606.120 Labeling, general requirements. 606.121 Container label. the collection, processing, compat- 606.122 Instruction circular. ibility testing, storage or distribution of blood and blood components. Subpart H—Laboratory Controls (i) Processing means any procedure employed after collection and before 606.140 Laboratory controls. compatibility testing of blood and in- 606.151 Compatibility testing. cludes the identification of a unit of Subpart I—Records and Reports donor blood, the preparation of compo- nents from such unit of donor blood, 606.160 Records. serological testing, labeling and associ- 606.165 Distribution and receipt; procedures ated recordkeeping. and records. (j) Compatibility testing means the in 606.170 Adverse reaction file. vitro serological tests performed on AUTHORITY: 21 U.S.C. 321, 331, 351, 352, 355, donor and recipient blood samples to 360, 360j, 371, 374; 42 U.S.C. 216, 262, 263a, 264. establish the serological matching of a SOURCE: 40 FR 53532, Nov. 18, 1975, unless donor’s blood or blood components otherwise noted. with that of a potential recipient.
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Subpart B—Organization and (3) The storage of blood or blood com- Personnel ponents pending completion of tests. (4) The quarantine storage of blood or § 606.20 Personnel. blood components in a designated loca- tion pending repetition of those tests (a) [Reserved] that initially gave questionable sero- (b) The personnel responsible for the logical results. collection, processing, compatibility (5) The storage of finished products testing, storage or distribution of blood prior to distribution. or blood components shall be adequate (6) The quarantine storage, handling in number, educational background, and disposition of products and re- training and experience, including pro- agents not suitable for use. fessional training as necessary, or com- (7) The orderly collection, processing, bination thereof, to assure competent compatibility testing, storage and dis- performance of their assigned func- tribution of blood and blood compo- tions, and to ensure that the final nents to prevent contamination. product has the safety, purity, po- (8) The adequate and proper perform- tency, identity and effectiveness it pur- ance of all steps in plasmapheresis, ports or is represented to possess. All plateletpheresis and leukapheresis pro- personnel shall have capabilities com- cedures. mensurate with their assigned func- tions, a thorough understanding of the (9) The orderly conduction of all procedures or control operations they packaging, labeling and other finishing perform, the necessary training or ex- operations. perience, and adequate information (b) Provide adequate lighting, ven- concerning the application of pertinent tilation and screening of open windows provisions of this part to their respec- and doors. tive functions. (c) Provide adequate, clean, and con- (c) Persons whose presence can ad- venient handwashing facilities for per- versely affect the safety and purity of sonnel, and adequate, clean, and con- the products shall be excluded from venient toilet facilities for donors and areas where the collection, processing, personnel. Drains shall be of adequate compatibility testing, storage or dis- size and, where connected directly to a tribution of blood or blood components sewer, shall be equipped with traps to is conducted. prevent back-siphonage. (d) Provide for safe and sanitary dis- [40 FR 53532, Nov. 18, 1975, as amended at 49 posal for the following: FR 23833, June 8, 1984; 55 FR 11014, Mar. 26, (1) Trash and items used during the 1990; 62 FR 53538, Oct. 15, 1997] collection, processing and compat- ibility testing of blood and blood com- Subpart C—Plant and Facilities ponents. (2) Blood and blood components not § 606.40 Facilities. suitable for use or distribution. Facilities shall be maintained in a clean and orderly manner, and shall be Subpart D—Equipment of suitable size, construction and loca- tion to facilitate adequate cleaning, § 606.60 Equipment. maintenance and proper operations. (a) Equipment used in the collection, The facilities shall: processing, compatibility testing, stor- (a) Provide adequate space for the age and distribution of blood and blood following when applicable: components shall be maintained in a (1) Private and accurate examina- clean and orderly manner and located tions of individuals to determine their so as to facilitate cleaning and mainte- suitability as blood donors. nance. The equipment shall be ob- (2) The withdrawal of blood from do- served, standardized and calibrated on nors with minimal risk of contamina- a regularly scheduled basis as pre- tion, or exposure to activities and scribed in the Standard Operating Pro- equipment unrelated to blood collec- cedures Manual and shall perform in tion. the manner for which it was designed
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so as to assure compliance with the of- (b) Equipment that shall be observed, ficial requirements prescribed in this standardized and calibrated with at chapter for blood and blood products. least the following frequency, include but are not limited to:
Equipment Performance check Frequency Frequency of calibration
Temperature recorder .... Compare against thermometer ...... Daily ...... As necessary. Refrigerated centrifuge .. Observe speed and temperature ...... Each day of use Do. Hematocrit centrifuge ...... Standardize before initial use, after re- pairs or adjustments, and annually. Timer every 3 mo. General lab centrifuge ...... Tachometer every 6 mo. Automated blood-typing Observe controls for correct results ..... Each day of use. machine. Hemoglobinometer ...... Standardize against ...... do ...... cyanmethemoglobin standard. Refractometer ...... Standardize against distilled water ...... do ...... Blood container scale .... Standardize against container of known ...... do ...... As necessary. weight. Water bath ...... Observe temperature ...... do ...... Do. Rh view box ...... do ...... do ...... Do. Autoclave ...... do ...... Each time of use Do. Serologic rotators ...... Observe controls for correct results ..... Each day of use Speed as necessary. Laboratory thermom- ...... Before initial use. eters. Electronic thermometers ...... Monthly. Vacuum blood agitator .. Observe weight of the first container of Each day of use Standardize with container of known blood filled for correct results. mass or volume before initial use, and after repairs or adjustments.
(c) Equipment employed in the steri- the product. All final containers and lization of materials used in blood col- closures for blood and blood compo- lection or for disposition of contami- nents not intended for transfusion nated products shall be designed, main- shall be clean and free of surface solids tained and utilized to ensure the de- and other contaminants. struction of contaminating microorga- (b) Each blood collecting container nisms. The effectiveness of the steri- and its satellite container(s), if any, lization procedure shall be no less than shall be examined visually for damage that achieved by an attained tempera- or evidence of contamination prior to ture of 121.5 °C (251 °F) maintained for its use and immediately after filling. 20 minutes by saturated steam or by an Such examination shall include inspec- attained temperature of 170 °C (338 °F) tion for breakage of seals, when indi- maintained for 2 hours with dry heat. cated, and abnormal discoloration. Where any defect is observed, the con- [40 FR 53532, Nov. 18, 1975; 40 FR 55849, Dec. 2, 1975, as amended at 45 FR 9261, Feb. 12, tainer shall not be used, or, if detected 1980; 57 FR 11263, Apr. 2, 1992; 57 FR 12862, after filling, shall be properly dis- Apr. 13, 1992] carded. (c) Representative samples of each § 606.65 Supplies and reagents. lot of the following reagents or solu- All supplies and reagents used in the tions shall be tested on a regularly collection, processing, compatibility scheduled basis by methods described testing, storage and distribution of in the Standard Operating Procedures blood and blood components shall be Manual to determine their capacity to stored in a safe, sanitary and orderly perform as required: manner. Reagent or solution Frequency of testing (a) All surfaces coming in contact with blood and blood components in- Anti-human globulin ...... Each day of use. tended for transfusion shall be sterile, Blood grouping reagents ...... Do. pyrogen-free, and shall not interact Lectins ...... Do. Antibody screening and re- Do. with the product in such a manner as verse grouping cells. to have an adverse effect upon the safe- Hepatitis test reagents ...... Each run. ty, purity, potency or effectiveness of Syphilis serology reagents .... Do.
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Reagent or solution Frequency of testing (2) Methods of performing donor qualifying tests and measurements, in- Enzymes ...... Each day of use. cluding minimum and maximum values for a test or procedure when a factor in (d) Supplies and reagents that do not determining acceptability. bear an expiration date shall be stored (3) Solutions and methods used to in such a manner that the oldest is prepare the site of phlebotomy to give used first. maximum assurance of a sterile con- (e) Supplies and reagents shall be tainer of blood. used in a manner consistent with in- (4) Method of accurately relating the structions provided by the manufac- product(s) to the donor. turer. (5) Blood collection procedure, in- (f) Items that are required to be ster- cluding in-process precautions taken to ile and come into contact with blood measure accurately the quantity of should be disposable whenever possible. blood removed from the donor. [40 FR 53532, Nov. 18, 1975, as amended at 59 (6) Methods of component prepara- FR 23636, May 6, 1994] tion, including any time restrictions for specific steps in processing. Subpart E [Reserved] (7) All tests and repeat tests per- formed on blood and blood components during processing, including testing for Subpart F—Production and hepatitis B surface antigen as pre- Process Controls scribed in § 610.40 of this chapter. (8) Pretransfusion testing, where ap- § 606.100 Standard operating proce- plicable, including precautions to be dures. taken to identify accurately the recipi- (a) In all instances, except clinical ent blood samples and crossmatched investigations, standard operating pro- donor units. cedures shall comply with published (9) Procedures for investigating ad- additional standards in part 640 of this verse donor and recipient reactions. chapter for the products being proc- (10) Storage temperatures and meth- essed; except that, references in part ods of controlling storage temperatures 640 relating to licenses, licensed estab- for all blood products and reagents as lishments and submission of material prescribed in §§ 600.15 and 610.53 of this or data to or approval by the Director, chapter. Center for Biologics Evaluation and (11) Length of expiration dates, if Research, are not applicable to estab- any, assigned for all final products as lishments not subject to licensure prescribed in § 610.53 of this chapter. under section 351 of the Public Health (12) Criteria for determining whether Service Act. returned blood is suitable for reissue. (b) Written standard operating proce- (13) Procedures used for relating a dures shall be maintained and shall in- unit of blood or blood component from clude all steps to be followed in the the donor to its final disposition. collection, processing, compatibility (14) Quality control procedures for testing, storage and distribution of supplies and reagents employed in blood and blood components for homol- blood collection, processing and ogous transfusion, autologous trans- pretransfusion testing. fusion and further manufacturing pur- (15) Schedules and procedures for poses. Such procedures shall be avail- equipment maintenance and calibra- able to the personnel for use in the tion. areas where the procedures are per- (16) Labeling procedures, including formed, unless this is impractical. The safeguards to avoid labeling mixups. written standard operating procedures (17) Procedures of plasmapheresis, shall include, but are not limited to, plateletpheresis, and leukapheresis, if descriptions of the following, when ap- performed, including precautions to be plicable: taken to ensure reinfusion of a donor’s (1) Criteria used to determine donor own cells. suitability, including acceptable med- (18) Procedure for preparing recov- ical history criteria. ered (salvaged) plasma, if performed,
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including details of separation, pool- (1) American Association of Blood ing, labeling, storage and distribution. Banks. (19) Procedures in accordance with (2) American National Red Cross. § 610.46 of this chapter to look at prior (3) Other organizations or individual donations of Whole Blood, blood com- blood banks, subject to approval by the ponents, Source Plasma and Source Director, Center for Biologics Evalua- Leukocytes from a donor who has do- tion and Research. nated blood and subsequently tests re- [40 FR 53532, Nov. 18, 1975, as amended at 49 peatedly reactive for antibody to FR 23833, June 8, 1984; 55 FR 11013, Mar. 26, human immunodeficiency virus (HIV) 1990; 61 FR 47422, Sept. 9, 1996] or otherwise is determined to be un- suitable when tested in accordance § 606.110 Plateletpheresis, with § 610.45 of this chapter. Procedures leukapheresis, and plasmapheresis. to quarantine in-house Whole Blood, (a) The use of plateletpheresis and blood components, Source Plasma and leukapheresis procedures to obtain a Source Leukocytes intended for further product for a specific recipient may be manufacture into injectable products at variance with the additional stand- that were obtained from such donors; ards for specific products prescribed in procedures to notify consignees regard- this part provided that: (1) A physician ing the need to quarantine such prod- has determined that the recipient must ucts; procedures to determine the suit- be transfused with the leukocytes or ability for release of such products platelets from a specific donor, and (2) from quarantine; procedures to notify the procedure is performed under the consignees of Whole Blood, blood com- supervision of a qualified licensed phy- ponents, Source Plasma and Source sician who is aware of the health sta- Leukocytes from such donors of the re- tus of the donor, and the physician has sults of the antibody testing of such certified in writing that the donor’s donors; and procedures in accordance health permits plateletpheresis or with § 610.47 of this chapter to notify leukapheresis. attending physicians so that trans- (b) Plasmapheresis of donors who do fusion recipients are informed that not meet the donor requirements of they may have received Whole Blood §§ 640.63, 640.64 and 640.65 of this chapter and, blood components at increased for the collection of plasma containing risk for transmitting human immuno- rare antibodies shall be permitted only deficiency virus. with the prior approval of the Director, (c) All records pertinent to the lot or Center for Biologics Evaluation and unit maintained pursuant to these reg- Research. ulations shall be reviewed before the release or distribution of a lot or unit [40 FR 53532, Nov. 18, 1975, as amended at 49 of final product. The review or portions FR 23833, June 8, 1984; 55 FR 11013, Mar. 26, 1990] of the review may be performed at ap- propriate periods during or after blood collecting, processing, compatibility Subpart G—Finished Product testing and storing. A thorough inves- Control tigation, including the conclusions and followup, of any unexplained discrep- § 606.120 Labeling, general require- ancy or the failure of a lot or unit to ments. meet any of its specifications shall be (a) Labeling operations shall be sepa- made and recorded. rated physically or spatially from (d) In addition to the requirements of other operations in a manner adequate this subpart and in conformity with to prevent mixups. this section, any facility may utilize (b) The labeling operation shall in- current standard operating procedures clude the following labeling controls: such as the manuals of the following (1) Labels shall be held upon receipt, organizations, as long as such specific pending review and proofing against an procedures are consistent with, and at approved final copy, to ensure accuracy least as stringent as, the requirements regarding identity, content, and con- contained in this part. formity with the approved copy.
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(2) Each type of label representing classification statement, i.e., ‘‘paid different products shall be stored and donor’’ or ‘‘volunteer donor’’, in no less maintained in a manner to prevent prominence than the proper name of mixups, and stocks of obsolete labels the product. shall be destroyed. (i) A paid donor is a person who re- (3) All necessary checks in labeling ceives monetary payment for a blood procedures shall be utilized to prevent donation. errors in translating test results to (ii) A volunteer donor is a person who container labels. does not receive monetary payment for (c) All labeling shall be clear and leg- a blood donation. ible. (iii) Benefits, such as time off from [50 FR 35469, Aug. 30, 1985] work, membership in blood assurance programs, and cancellation of non- § 606.121 Container label. replacement fees that are not readily (a) The container label requirements convertible to cash, do not constitute are designed to facilitate the use of a monetary payment within the meaning uniform container label for blood and of this paragraph. blood components (except Source Plas- (6) For Whole Blood, Plasma, Plate- ma) by all blood establishments. Single lets, and partial units of Red Blood copies of an FDA guideline entitled Cells, the volume of the product, accu- ‘‘Guideline for the Uniform Labeling of rate to within ±10 percent; or option- Blood and Blood Components’’ are ally for Platelets, the volume range available upon request (under Docket within reasonable limits. No. 80N–0120) from the Dockets Man- (7) The recommended storage tem- agement Branch (HFA–305), Food and perature (in degrees Celsius). Drug Administration, Rm. 1–23, 12420 (8) If the product is intended for Parklawn Dr., Rockville, MD 20857 transfusion, the statements: (copies of the guideline are available (i) ‘‘Caution: Federal law prohibits also from the American Blood Commis- dispensing without prescription.’’ sion, 1901 North Ft. Myer Drive, Suite (ii) ‘‘See circular of information for 300, Arlington, VA 22209). indications, contraindications, cau- (b) The label provided by the col- tions, and methods of infusion.’’ lecting facility and the initial proc- (iii) ‘‘Properly identify intended re- essing facility shall not be removed, al- cipient.’’ tered, or obscured, except that the (9) The statement: ‘‘This product label may be altered to indicate the may transmit infectious agents.’’ proper name and other information re- quired to identify accurately the con- (10) Where applicable, the name and tents of a container after blood compo- volume of source material. nents have been prepared. (11) The statement: ‘‘Caution: For (c) The container label shall include Manufacturing Use Only’’, when appli- the following information, as well as cable. other specialized information as re- (12) If the product is intended for quired in this section for specific prod- transfusion, the ABO and Rh groups of ucts: the donor shall be designated conspicu- (1) The proper name of the product in ously. For Cryoprecipitated AHF, the a prominent position, and modifier(s), Rh group may be omitted. The Rh if appropriate. group shall be designated as follows: (2) The name, address, registration (i) If the test using Anti-D Blood number, and, if a licensed product, the Grouping Reagent is positive, the prod- license number of each manufacturer. uct shall be labeled: ‘‘Rh positive.’’ (3) The donor, pool, or lot number re- (ii) If the test using Anti-D Blood lating the unit to the donor. Grouping Reagent is negative but the (4) The expiration date, including the test for Du is positive, the product shall day, month, and year, and, if the dat- be labeled: ‘‘Rh positive.’’ ing period for the product is 72 hours or (iii) If the test using Anti-D Blood less, the hour of expiration. Grouping Reagent is negative and the (5) If the product is intended for test for Du is negative, the product transfusion, the appropriate donor shall be labeled: ‘‘Rh negative.’’
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(13) The container label may bear en- (e) CP2D, or by other nomenclature ap- coded information in the form of ma- proved for use by the Director, Office of chine-readable symbols approved for Biologics Research and Review (HFN– use by the Director, Center for Bio- 800), Center for Drugs and Biologics. logics Evaluation and Research (HFB– (iii) If tests for unexpected antibodies 1). are positive, blood intended for trans- (d) Except for recovered plasma in- fusion shall be labeled: ‘‘Contains tended for manufacturing use or as (name of antibody).’’ otherwise approved by the Director, (2) Except for frozen, deglycerolized, Center for Biologics Evaluation and or washed Red Blood Cell products, red Research (HFB–1), the paper of the con- blood cell labels shall include: tainer label shall be white and print (i) The volume and kind of Whole shall be solid black, with the following Blood, including the type of anticoagu- additional exceptions: lant, from which the product was pre- (1) The Rh blood group shall be print- pared. ed as follows: (ii) If tests for unexpected antibodies (i) Rh positive: Use black print on are positive and the product is in- white background. tended for transfusion, the statement: (ii) Rh negative: Use white print on ‘‘Contains (name of antibody).’’ black background. (2) The proper name of the product, (3) Labels for products with a dating any appropriate modifier(s), the donor period of 72 hours or less, including any classification statement, and the state- product prepared in a system that may ment ‘‘properly identify intended re- compromise sterility, shall bear the cipient’’ shall be printed in solid red. hour of expiration. (3) The following color scheme may (4) If tests for unexpected antibodies be used optionally for differentiating are positive, Plasma intended for ABO Blood groups: transfusion shall be labeled: ‘‘Contains (name of antibody).’’ Blood group Color of label paper (5) Recovered plasma labels shall in- O Blue clude: A Yellow (i) In lieu of an expiration date, the B Pink date of collection of the oldest mate- AB White rial in the container. (4) Ink colors used for the optional (ii) The statement: ‘‘Caution: For color coding system described in para- Manufacturing Use Only’’; or ‘‘Caution: graph (d)(3) of this section shall be a For Use in Manufacturing visual match to specific color samples Noninjectable Products Only’’, as ap- designated by the Director, Center for plicable. Biologics Evaluation and Research (iii) For recovered plasma not meet- (HFB–1). ing the requirements for manufacture (5) Special labels, such as those de- into licensable products, the state- scribed in paragraphs (h) and (i) of this ment: ‘‘Not for Use in Products Subject section, may be color coded using the to License Under Section 351 of the colors recommended in the guideline Public Health Service Act.’’ (see paragraph (a) of this section), or (f) Blood and blood components de- colors otherwise approved for use by termined to be unsuitable for trans- the Director, Center for Biologics Eval- fusion shall be prominently labeled: uation and Research (HFB–1). ‘‘NOT FOR TRANSFUSION’’, and the (e) Container label requirements for label shall state the reason the unit is particular products or groups of prod- considered unsuitable. The provision ucts. does not apply to recovered plasma la- (1) Whole Blood labels shall include: beled according to paragraph (e)(5) of (i) The volume of anticoagulant. this section. (ii) The name of the applicable anti- (g) As required under § 610.40 of this coagulant immediately preceding and chapter, labels for blood and blood of no less prominence than the proper components that are reactive for Hepa- name and expressed as follows: (a) titis B Surface Antigen, but that are ACD, (b) CPD, (c) Heparin, (d) CPDA–1, intended for further manufacturing,
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shall state conspicuously that the ma- (j) A tie-tag attached to the con- terial is reactive when tested for hepa- tainer may be used for providing the titis B surface antigen and may trans- information required by paragraph (e) mit viral hepatitis or, as applicable, (1)(iii), (2)(ii), and (4), (h), or (i)(1), (2), that blood was collected from a donor and (3) of this section. known to be reactive for hepatitis B [50 FR 35469, Aug. 30, 1985, as amended at 53 surface antigen and is presumed to be FR 116, Jan. 5, 1988; 55 FR 11014, Mar. 26, 1990; infectious, although confirmatory hep- 57 FR 10814, Mar. 31, 1992; 59 FR 23636, May 6, atitis testing has not been done. 1994; 63 FR 16685, Apr. 6, 1998]
(h) The following additional informa- EFFECTIVE DATE NOTE: The information tion shall appear on the label for blood collection requirements contained in § 606.121 or blood components shipped in an will not become effective until OMB ap- emergency, prior to completion of re- proval has been obtained. FDA will publish a quired tests, in accordance with notice of OMB approval in the FEDERAL REG- § 640.2(f) of this chapter: ISTER. (1) The statement: ‘‘FOR EMER- § 606.122 Instruction circular. GENCY USE ONLY BY llll.’’ (2) Results of any tests prescribed An instruction circular shall be under §§ 610.40, 610.45, and 640.5 (a), (b), available for distribution if the product or (c) of this chapter completed before is intended for transfusion. The in- shipment. struction circular shall provide ade- quate directions for use, including the (3) Indication of any tests prescribed following information: under §§ 610.40, 610.45, and 640.5 (a), (b), (a) Instructions to mix the product or (c) of this chapter and not completed before use. before shipment. (b) Instructions to use a filter in the (i) The following additional informa- administration equipment. tion shall appear on the label for Whole (c) The statement ‘‘Do Not Add Medi- Blood or Red Blood Cells intended for cations’’ or an explanation concerning autologous infusion: allowable additives. (1) Information adequately identi- (d) A description of the product, its fying the patient, e.g., name, blood source, and preparation, including the group, hospital, and identification name and proportion of the anticoagu- number. lant used in collecting the Whole Blood (2) Date of donation. from each product is prepared. (3) The statement: ‘‘FOR (e) Statements that the product was AUTOLOGOUS USE ONLY.’’ prepared from blood that was negative (4) In place of the blood group label, when tested for antibody to Human Im- each container of blood intended for munodeficiency Virus (HIV) and non- autologous use and obtained from a reactive for hepatitis B surface antigen donor who fails to meet any of the by FDA required tests and nonreactive donor suitability requirements under when tested for syphilis by a serologic § 640.3 of this chapter or who is reactive test for syphilis (STS). in the hepatitis tests prescribed under (f) The statements: ‘‘Warning. The § 610.40 of this chapter shall be promi- risk of transmitting hepatitis is nently and permanently labeled: ‘‘FOR present. Careful donor selection and AUTOLOGOUS USE ONLY.’’ available laboratory tests do not elimi- (5) Units of blood originally intended nate the hazard.’’ for autologous use, except those la- (g) The names of cryoprotective beled as prescribed under paragraph agents and other additives that may (i)(4) of this section, may be issued for still be present in the product. homologous transfusion provided the (h) The names and results of all tests container label complies with all appli- performed when necessary for safe and cable provisions of paragraphs (b) effective use. through (e) of this section. In such (i) The use of the product, indica- case, the special label required under tions, contradications, side effects and paragraph (i) (1), (2), and (3) of this sec- hazards, dosage and administration tion shall be removed or otherwise ob- recommendations. scured. (j) [Reserved]
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(k) For Red Blood Cells, the instruc- (6) A statement that 0.9 percent So- tion circular shall contain: dium Chloride Injection U.S.P. is the (1) Instructions to administer a suit- preferred diluent. able plasma volume expander if Red (7) Adequate instructions for pooling Blood Cells are substituted when Whole to ensure complete removal of all con- Blood is the indicated product. centrated material from each con- (2) A warning not to add Lactated tainer. Ringer’s Injection U.S.P. solution to (8) The statement: ‘‘Good patient Red Blood Cell products. management requires monitoring (l) For Platelets, the instruction cir- treatment responses to cular shall contain: Cryoprecipitated AHF transfusions (1) The approximate volume of plas- with periodic plasma factor VIII or ma from which a sample unit of Plate- fibrinogen assays in hemophilia A and lets is prepared. hypofibrinogenemic recipients, respec- tively.’’ (2) Instructions to begin administra- tion as soon as possible, but not more [50 FR 35470, Aug. 30, 1985, as amended at 53 than 4 hours after entering the con- FR 116, Jan. 5, 1988] tainer. EFFECTIVE DATE NOTE: The information (m) For Plasma, the instruction cir- collection requirements contained in § 606.122 cular shall contain: will not become effective until OMB ap- (1) A warning against further proc- proval has been obtained. FDA will publish a notice of OMB approval in the FEDERAL REG- essing of the frozen product if there is ISTER. evidence of breakage or thawing. (2) Instructions to thaw the frozen product at a temperature between 30 Subpart H—Laboratory Controls ° and 37 C. § 606.140 Laboratory controls. (3) When applicable, instructions to Laboratory control procedures shall begin administration of the product include: within 6 hours after thawing. (a) The establishment of scientif- (4) Instructions to administer to ically sound and appropriate specifica- ABO-group-compatible recipients. tions, standards and test procedures to (5) A statement that this product has assure that blood and blood compo- the same hepatitis risk as Whole Blood; nents are safe, pure, potent and effec- other plasma volume expanders with- tive. out this risk are available for treating (b) Adequate provisions for moni- hypovolemia. toring the reliability, accuracy, preci- (n) For Cryoprecipitated AHF, the in- sion and performance of laboratory struction circular shall contain: test procedures and instruments. (1) A statement that the average po- (c) Adequate identification and han- tency is 80 or more International Units dling of all test samples so that they of antihemophilic factor. are accurately related to the specific (2) The statement: ‘‘Usually contains unit of product being tested, or to its at least 150 milligrams of fibrinogen’’; donor, or to the specific recipient, or, alternatively, the average where applicable. fibrinogen level determined by assay of representative units. § 606.151 Compatibility testing. (3) A warning against further proc- Standard operating procedures for essing of the product if there is evi- compatibility testing shall include the dence of breakage or thawing. following: (4) Instructions to thaw the product (a) A method of collecting and identi- for no more than 15 minutes at a tem- fying the blood samples of recipients to perature of 37 °C. ensure positive identification. (5) Instructions to store at room tem- (b) The use of fresh recipient serum perature after thawing and to begin ad- samples less than 48 hours old for all ministration as soon as possible but no pretransfusion testing. more than 4 hours after entering the (c) The testing of the donor’s cells container or after pooling and within 6 with the recipient’s serum (major hours after thawing. crossmatch) by a method that will
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demonstrate agglutinating, coating cians, the donor’s disease and disposi- and hemolytic antibodies, which shall tion of units. include the antiglobulin method. (v) Immunization, including informed (d) A provision that, if the unit of do- consent, identification of the antigen, nor’s blood has not been screened by a dosage and route of administration. method that will demonstrate aggluti- (vi) Blood collection, including iden- nating, coating and hemolytic anti- tification of the phlebotomist. bodies, the recipient’s cells shall be (vii) Records to relate the donor with tested with the donor’s serum (minor the unit number of each previous dona- crossmatch) by a method that will so tion from that donor. demonstrate. (viii) Records of quarantine, notifica- (e) Procedures to expedite trans- tion, testing, and disposition performed fusions in life-threatening emer- pursuant to §§ 610.46 and 610.47 of this gencies. Records of all such incidents chapter. shall be maintained, including com- (2) Processing records: plete documentation justifying the emergency action, which shall be (i) Blood processing, including results signed by the physician requesting the and interpretation of all tests and procedure. retests. (ii) Component preparation, includ- Subpart I—Records and Reports ing all relevant dates and times. (iii) Separation and pooling of recov- § 606.160 Records. ered plasma. (a)(1) Records shall be maintained (iv) Centrifugation and pooling of concurrently with the performance of source plasma. each significant step in the collection, (v) Labeling, including initials of per- processing, compatibility testing, stor- son(s) responsible. age and distribution of each unit of (3) Storage and distribution records: blood and blood components so that all (i) Distribution and disposition, as steps can be clearly traced. All records appropriate, of blood and blood prod- shall be legible and indelible, and shall ucts. identify the person performing the (ii) Visual inspection of whole blood work, include dates of the various en- and red blood cells during storage and tries, show test results as well as the immediately before distribution. interpretation of the results, show the (iii) Storage temperature, including expiration date assigned to specific initialed temperature recorder charts. products, and be as detailed as nec- (iv) Reissue, including records of essary to provide a complete history of proper temperature maintenance. the work performed. (v) Emergency release of blood, in- (2) Appropriate records shall be avail- cluding signature of requesting physi- able from which to determine lot num- cian obtained before or after release. bers of supplies and reagents used for (4) Compatibility test records: specific lots or units of the final prod- (i) Results of all compatibility tests, uct. including crossmatching, testing of pa- (b) Records shall be maintained that tient samples, antibody screening and include, but are not limited to, the fol- identification. lowing when applicable: (ii) Results of confirmatory testing. (1) Donor records: (5) Quality control records: (i) Donor selection, including medical interview and examination and where (i) Calibration and standardization of applicable, informed consent. equipment. (ii) Permanent and temporary defer- (ii) Performance checks of equipment rals for health reasons including rea- and reagents. son(s) for deferral. (iii) Periodic check on sterile tech- (iii) Donor adverse reaction com- nique. plaints and reports, including results of (iv) Periodic tests of capacity of ship- all investigations and followup. ping containers to maintain proper (iv) Therapeutic bleedings, including temperature in transit. signed requests from attending physi- (v) Proficiency test results.
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(6) Transfusion reaction reports and identification of the name and address complaints, including records of inves- of the consignee, the date and quantity tigations and followup. delivered, the lot number of the unit(s), (7) General records: the date of expiration or the date of (i) Sterilization of supplies and re- collection, whichever is applicable, or agents prepared within the facility, in- for crossmatched blood and blood com- cluding date, time interval, tempera- ponents, the name of the recipient. ture and mode. (c) Receipt records shall contain the (ii) Responsible personnel. name and address of the collecting fa- (iii) Errors and accidents. cility, date received, donor or lot num- (iv) Maintenance records for equip- ber assigned by the collecting facility ment and general physical plant. and the date of expiration or the date (v) Supplies and reagents, including of collection, whichever is applicable. name of manufacturer or supplier, lot numbers, expiration date and date of § 606.170 Adverse reaction file. receipt. (vi) Disposition of rejected supplies (a) Records shall be maintained of and reagents used in the collection, any reports of complaints of adverse processing and compatibility testing of reactions regarding each unit of blood blood and blood components. or blood product arising as a result of (c) A donor number shall be assigned blood collection or transfusion. A thor- to each accepted donor, which relates ough investigation of each reported ad- the unit of blood collected to that verse reaction shall be made. A written donor, to his medical record, to any report of the investigation of adverse component or blood product from that reactions, including conclusions and donor’s unit of blood, and to all records followup, shall be prepared and main- describing the history and ultimate tained as part of the record for that lot disposition of these products. or unit of final product by the col- (d) Records shall be retained for such lecting or transfusing facility. When it interval beyond the expiration date for is determined that the product was at the blood or blood component as nec- fault in causing a transfusion reaction, essary to facilitate the reporting of copies of all such written reports shall any unfavorable clinical reactions. The be forwarded to and maintained by the retention period shall be no less than 5 manufacturer or collecting facility. years after the records of processing (b) When a complication of blood col- have been completed or 6 months after lection or transfusion is confirmed to the latest expiration date for the indi- be fatal, the Director, Office of Compli- vidual product, whichever is a later ance, Center for Biologics Evaluation date. When there is no expiration date, and Research, shall be notified by tele- records shall be retained indefinitely. phone or telegraph as soon as possible; (e) A record shall be available from a written report of the investigation which unsuitable donors may be identi- shall be submitted to the Director, Of- fied so that products from such individ- uals will not be distributed. fice of Compliance, Center for Biologics Evaluation and Research, within 7 days [40 FR 53532, Nov. 18, 1975, as amended at 61 after the fatality by the collecting fa- FR 47422, Sept. 9, 1996] cility in the event of a donor reaction, or by the facility that performed the § 606.165 Distribution and receipt; pro- cedures and records. compatibility tests in the event of a transfusion reaction. (a) Distribution and receipt proce- dures shall include a system by which (Information collection requirements ap- the distribution or receipt of each unit proved by the Office of Management and can be readily determined to facilitate Budget under control number 0910–0116) its recall, if necessary. [40 FR 53532, Nov. 18, 1975, as amended at 49 (b) Distribution records shall contain FR 23833, June 8, 1984; 50 FR 35471, Aug. 30, information to readily facilitate the 1985; 55 FR 11014, Mar. 26, 1990]
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