(h) "Facilities” means any area used for the collection, processing, compatibility testing, storage or distribution of blood and blood components.

(i) "Processing" means any procedure employed after collection and before compatibility testing of blood and includes the identification of a unit of donor blood, the preparation of components from such unit of donor blood, serological testing, labeling and associated recordkeeping.

(j) "Compatibility testing" means the in vitro serological tests performed on donor and recipient blood samples to establish the serological matching of a donor's blood or blood components with that of a potential recipient.

(a) A blood establishment shall be under the direction of a designated, qualified person who shall exercise control of the establishment in all matters relating to compliance with the provisions of this subchapter. This person shall also have the authority to represent the establishment in all pertinent matters with the Center for Biologics Evaluation and Research and to enforce, or direct the enforcement of, discipline and the performance of assigned functions by employees engaged in the collection, processing, compatibility testing, storage and distribution of blood and blood components. The designated director shall have an understanding of the scientific principles and techniques involved in the manufacture of blood products and shall have the responsibility for ensuring that employees are adequately trained in standard operating procedures and that they are aware of the application of the pertinent provisions of this chapter to their respective functions.

(b) The personnel responsible for the collection, processing, compatibility testing, storage or distribution of blood or blood components shall be adequate in number, educational background, training and experience, including professional training as necessary, or combination thereof, to assure

competent performance of their assigned functions, and to ensure that the final product has the safety, purity, potency, identity and effectiveness it purports or is represented to possess. All personnel shall have capabilities commensurate with their assigned functions, a thorough understanding of the procedures or control operations they perform, the necessary training or experience, and adequate information concerning the application of pertinent provisions of this part to their respective functions.

(c) Persons whose presence can adversely affect the safety and purity of the products shall be excluded from areas where the collection, processing, compatibility testing, storage or distribution of blood or blood components is conducted.

[40 FR 53532, Nov. 18, 1975, as amended at 49 FR 23833, June 8, 1984; 55 FR 11014, Mar. 26, 1990]

Subpart C-Plant and Facilities

§ 606.40 Facilities.

Facilities shall be maintained in a clean and orderly manner, and shall be of suitable size, construction and location to facilitate adequate cleaning, maintenance and proper operations. The facilities shall:

(a) Provide adequate space for the following when applicable:

(1) Private and accurate examinations of individuals to determine their suitability as blood donors.

(2) The withdrawal of blood from donors with minimal risk of contamination, or exposure to activities and equipment unrelated to blood collection.

(3) The storage of blood or blood components pending completion of tests.

(4) The quarantine storage of blood or blood components in a designated location pending repetition of those tests that initially gave questionable serological results.

(5) The storage of finished products prior to distribution.

(6) The quarantine storage, handling and disposition of products and reagents not suitable for use.

(7) The orderly collection, processing, compatibility testing, storage and distribution of blood and blood components to prevent contamination.

(8) The adequate and proper performance of all steps in plasmapheresis, plateletpheresis and leukapheresis procedures.

(9) The orderly conduction of all packaging, labeling and other finishing operations.

(b) Provide adequate lighting, ventilation and screening of open windows and doors.

(c) Provide adequate, clean, and convenient handwashing facilities for personnel, and adequate, clean, and convenient toilet facilities for donors and personnel. Drains shall be of adequate size and, where connected directly to a sewer, shall be equipped with traps to prevent back-siphonage.

(d) Provide for safe and sanitary disposal for the following:

(1) Trash and items used during the collection, processing and compatibility testing of blood and blood components.

Equipment

(2) Blood and blood components not suitable for use or distribution.

Subpart D-Equipment

§ 606.60 Equipment.

(a) Equipment used in the collection, processing, compatibility testing, storage and distribution of blood and blood components shall be maintained in a clean and orderly manner and located so as to facilitate cleaning and maintenance. The equipment shall be observed, standardized and calibrated on a regularly scheduled basis as prescribed in the Standard Operating Procedures Manual and shall perform in the manner for which it was designed so as to assure compliance with the official requirements prescribed in this chapter for blood and blood products.

(b) Equipment that shall be observed, standardized and calibrated with at least the following frequency, include but are not limited to:

Temperature recorder...... Compare against thermometer Refrigerated centrifuge.... Observe speed and temperature. Hematocrit centrifuge.

Frequency of calibration

As necessary. Do.

Standardize before initial use, after repairs or adjustments, and annually. Timer every 3 mo. Tachometer every 6 mo.

As necessary.

known weight.

......do

.do..

..do

Do. Do.

C (338° F) maintained for 2 hours with dry heat.

[40 FR 53532, Nov. 18, 1975; 40 FR 55849, Dec. 2, 1975, as amended at 45 FR 9261, Feb. 12, 1980]

§ 606.65 Supplies and reagents.

All supplies and reagents used in the collection, processing, compatibility testing, storage and distribution of blood and blood components shall be stored in a safe, sanitary and orderly

manner.

(a) All surfaces coming in contact with blood and blood components intended for transfusion shall be sterile, pyrogen-free, and shall not interact with the product in such a manner as to have an adverse effect upon the safety, purity, potency or effectiveness of the product. All final containers and closures for blood and blood components not intended for transfusion shall be clean and free of surface solids and other contaminants.

(b) Each blood collecting container and its satellite container(s), if any, shall be examined visually for damage or evidence of contamination prior to its use and immediately after filling. Such examination shall include inspection for breakage of seals, when indicated, and abnormal discoloration. Where any defect is observed, the container shall not be used, or, if detected after filling, shall be properly discarded.

(c) Representative samples of each lot of the following reagents or solutions shall be tested on a regularly scheduled basis by methods described in the Standard Operating Procedures Manual to determine their capacity to perform as required:

(e) Supplies and reagents shall be used in a manner consistent with instructions provided by the manufacturer.

(f) Items that are required to be sterile and come into contact with blood should be disposable whenever possible.

Subpart E-[Reserved]

Subpart F-Production and Process Controls

§ 606.100 Standard operating procedures. (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 homologous transfusion, autologous transfusion and further manufacturing purposes. Such procedures shall be available to the personnel for use in the areas where the procedures are performed, unless this is impractical. 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 processing, including testing for hepatitis B surface antigen as prescribed in § 610.40 of this chapter.

(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) Procedure for preparing recovered (salvaged) plasma, if performed, including details of separation, pooling, labeling, storage and distribution.

(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 por

tions 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 following 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]

§ 606.110 Plateletpheresis, leukapheresis, and plasmapheresis.

(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]

Subpart G-Finished Product Control

§ 606.120 Labeling, general requirements.

(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. Single copies of an FDA guideline entitled "Guideline for the Uniform Labeling of Blood and Blood Components" are available upon request (under Docket No. 80N-0120) from the Dockets Management Branch (HFA-305), Food and Drug Administration, Rm. 462, 5600 Fishers Lane, Rockville, MD 20857 (copies of the guideline are available also from the American Blood Commission, 1901 North Ft. Myer Drive, Suite 300, Arlington, VA 22209).

(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

re

other specialized information as quired 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) "Caution: Federal law prohibits dispensing without prescription."

(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 appli

cable.