The following question was sent to the e-Network for discussion:

"Prior to the release of products into distribution, are blood collecting facilities (both donor centers and hospital-based donor centers) requiring the QA unit to review all records prior to the release (refer to 21 CFR 211.192)? If so, are you willing to share the description of how this process is performed?"

Here are replies from some hospital transfusion services (some may also collect blood):

Hospital #1: We do not have a QA person review all the records before release. This is in the CFR 212's and largely impractical for a hospital. We could not get a syringe out the door before it outdated unless we made every person on staff the QA person for everyone else.

Hospital #2: YES - all records are reviewed prior to issue although not by the QA unit per se (one might say by individuals serving as QA unit agents).

Hospital #3: I work as the Laboratory Coordinator for Quality Assurance at a large hospital complex in Texas. The section of Code of Federal Regulation, Title 21, Section 211 refers to "Current Good Manufacturing Practice for Finished Pharmaceuticals", and in our opinion does not apply to the production of blood components. Below you'll find the text of the regulation we feel is the appropriate guideline for blood banks. Please let us know if you hear from others with similar, or differing opinions regarding this area, we're always open to learning new things.

[Code of Federal Regulations] [Title 21, Volume 7, Parts 600 to 799] [Revised as of April 1, 2000] From the U.S. Government Printing Office via GPO Access [CITE: 21CFR606] [Page 42-44]

TITLE 21--FOOD AND DRUGS

PART 606--CURRENT GOOD MANUFACTURING PRACTICE FOR BLOOD AND BLOOD COMPONENTS
--Table of Contents

Subpart F--Production and Process Controls

Sec. 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 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 Secs. 600.15 and 610.53 of this chapter.
(11) Length of expiration dates, if any, assigned for all final products as prescribed in Sec. 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 mix ups.
(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 Sec. 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 Sec. 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 Sec. 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.

(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 follow-up, 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] [[Page 44]]

Sec. 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 Secs. 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]

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Ira A. Shulman, MD
CBBS e-Network Forum Editor & Moderator