PART 606 CURRENT GOOD MANUFACTURING PRACTICE FOR BLOOD AND BLOOD

COMPONENTS

Authority: Secs. 201, 301, 501, 502, 505, 510, 520, 701, 704

of the Federal Food, Drug, and Cosmetic Act (21 U.S.C. 321, 331,

351, 352, 355, 360, 360j, 371, 374); secs. 215, 351, 353, 361 of

the Public Health Service Act (42 U.S.C. 216, 262, 263a, 264).

Source: 40 FR 53532, Nov. 18, 1975, unless otherwise noted.

Subpart A General Provisions

Section 606.3 Definitions.

As used in this part:

(a) Blood means whole blood collected from a single donor

and processed either for transfusion or further manufacturing.

(b) Unit means the volume of blood or one of its components

in a suitable volume of anticoagulant obtained from a single

collection of blood from one donor.

blood separated by physical or mechanical means.

(d) Plasma for further manufacturing means that liquid

portion of blood separated and used as material to prepare

another product.

(e) Plasmapheresis means the procedure in which blood is

removed from the donor, the plasma is separated from the formed

elements and at least the red blood cells are returned to the

donor. This process may be immediately repeated, once.

(f) Plateletpheresis means the procedure in which blood is

removed from the donor, a platelet concentrate is separated, and

the remaining formed elements and residual plasma are returned to

the donor.

(g) Leukapheresis means the procedure in which blood is

removed from the donor, a leukocyte concentrate is separated, and

the remaining formed elements and residual plasma are returned to

the donor.

(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.

Subpart B Organization and Personnel

Section 606.20 Personnel.

(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.

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

Section 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.

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.

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

distribution.

Subpart D Equipment

Section 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:

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 ... ...Ý Standardize before initial use,

after repairs or adjustments, and annually ... Timer every 3 mo.

General lab centrifuge ... ... ... Tachometer every 6 mo.

Automated blood-typing machine ... Observe controls for correct

results ... Each day of use.

Hemoglobinometer ... Standardize against cyanmethemoglobin

standard ... ... do

Refractometer ... Standardize against distilled water ... ...

do.

Blood container ... Standardize against container scale of known

weight ... do ... As necessary.

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 thermometers ... ... Before initial use.

Electronic thermometers ... ... ... Monthly.

Vacuum blood agitator ... Observe weight of the first container

of blood filled for correct results ... Each day of use ...

Standardize with container of known mass or volume before initial

use, and after repairs or adjustments.

used in blood collection or for disposition of contaminated

products shall be designed, maintained and utilized to ensure the

destruction of contaminating microorganisms. The effectiveness of

the sterilization procedure shall be no less than that achieved

by an attained temperature of 121.5ø C (251ø F) maintained for 20

minutes by saturated steam or by an attained temperature of 170ø

C (338ø 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; 57 FR 11263, Apr. 2, 1992;

57 FR 12862, Apr. 13, 1992]

Section 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.

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:

-------------------------------------------------------------

Reagent or solution Ý Frequency of testing

----------------------------+--------------------------------

Anti-human globulin........Ý Each day of use.

Blood grouping reagents....Ý Do.

Lectins....................Ý Do.

Antibody screening and Ý Do.

reverse grouping cells. Ý

Hepatitis test reagents.....Ý Each run.

Syphilis serology reagents.Ý Do.

Enzymes....................Ý Each day of use.

------------------------------------------------------------

(d) Supplies and reagents that do not bear an expiration

date shall be stored in such a manner that the oldest is used

first.

(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

Section 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 Section 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

Sections 600.15 and 610.53 of this chapter.

(11) Length of expiration dates, if any, assigned for all

final products as prescribed in Section 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.

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

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]

Section 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 Sections 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

Section 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.

[50 FR 35469, Aug. 30, 1985]

Section 606.121 Container label.

(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. 1-23, 12420 Parklawn Dr., 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.

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

ñ10 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 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 may bear encoded information in the

form of machine-readable symbols approved for use by the

Director, Center for Biologics Evaluation and Research (HFB-1).

(d) Except for recovered plasma intended for manufacturing

use or as otherwise approved by the Director, Center for

Biologics Evaluation and Research (HFB-1), 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.

(3) The following color scheme may be used optionally for

differentiating ABO Blood groups:

----------------------------

Ý Color of

Blood group Ý label

Ý paper

-------------+-------------

O Ý Blue.

A Ý Yellow.

B Ý Pink.

AB Ý White.

----------------------------

(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 (HFB-1).

(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 (HFB-1).

(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 and

expressd as follows: (a) ACD, (b) CPD, (c) Heparin, (d) CPDA-1,

(e) CP2D, or by other nomenclature approved for use by the

Director, Office of Biologics Research and Review (HFN-800),

Center for Drugs and Biologics.

(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: "Caution: For Manufacturing Use Only";

or "Caution: For Use in Manufacturing Noninjectable Products

Only", as applicable.

(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) As required under Section 610.40 of this chapter, labels

for blood and blood components that are reactive for Hepatitis B

Surface Antigen, but that are intended for further manufacturing,

shall state conspicuously that the material is reactive when

tested for hepatitis B surface antigen and may transmit viral

hepatitis or, as applicable, that blood was collected from a

donor known to be reactive for hepatitis B surface antigen and is

presumed to be infectious, although confirmatory hepatitis

testing has not been done.

(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 Section

640.2(f) of this chapter:

(1) The statement: "FOR EMERGENCY USE ONLY BY ____."

(2) Results of any tests prescribed under Sections 610.40,

610.45, and 640.5 (a), (b), or (c) of this chapter completed

before shipment.

(3) Indication of any tests prescribed under Sections

610.40, 610.45, 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

Section 640.3 of this chapter or who is reactive in the hepatitis

tests prescribed under Section 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]

Effective Date Note: The information collection requirements

contained in Section 606.121 will not become effective until OMB

approval has been obtained. FDA will publish a notice of OMB

approval in the Federal Register.

Section 606.122 Instruction circular.

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.

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

hepatitis 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 øC.

(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 37 øC.

(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]

Effective Date Note: The information collection requirements

contained in Section 606.122 will not become effective until OMB

approval has been obtained. FDA will publish a notice of OMB

approval in the Federal Register.

Subpart H Laboratory Controls

Section 606.140 Laboratory controls.

Laboratory control procedures shall include:

(a) The establishment of scientifically sound and

appropriate specifications, standards and test procedures to

assure that blood and blood components are safe, pure, potent and

effective.

(b) Adequate provisions for monitoring the reliability,

accuracy, precision and performance of laboratory test procedures

and instruments.

so that they are accurately related to the specific unit of

product being tested, or to its donor, or to the specific

recipient, where applicable.

Section 606.151 Compatibility testing.

Standard operating procedures for compatibility testing

shall include the following:

(a) A method of collecting and identifying the blood samples

of recipients to ensure positive identification.

(b) The use of fresh recipient serum samples less than 48

hours old for all pretransfusion testing.

serum (major crossmatch) by a method that will demonstrate

agglutinating, coating and hemolytic antibodies, which shall

include the antiglobulin method.

(d) A provision that, if the unit of donor's blood has not

been screened by a method that will demonstrate agglutinating,

coating and hemolytic antibodies, the recipient's cells shall be

tested with the donor's serum (minor crossmatch) by a method that

will so demonstrate.

(e) Procedures to expedite transfusions in life-threatening

emergencies. Records of all such incidents shall be maintained,

including complete documentation justifying the emergency action,

which shall be signed by the physician requesting the procedure.

Subpart I Records and Reports

Section 606.160 Records.

(a)(1) Records shall be maintained concurrently with the

performance of each significant step in the collection,

processing, compatibility testing, storage and distribution of

each unit of blood and blood components so that all steps can be

clearly traced. All records shall be legible and indelible, and

shall identify the person performing the work, include dates of

the various entries, show test results as well as the

interpretation of the results, show the expiration date assigned

to specific products, and be as detailed as necessary to provide

a complete history of the work performed.

(2) Appropriate records shall be available from which to

determine lot numbers of supplies and reagents used for specific

lots or units of the final product.

(b) Records shall be maintained that include, but are not

limited to, the following when applicable:

(1) Donor records:

(i) Donor selection, including medical interview and

examination and where applicable, informed consent.

(ii) Permanent and temporary deferrals for health reasons

including reason(s) for deferral.

(iii) Donor adverse reaction complaints and reports,

including results of all investigations and followup.

(iv) Therapeutic bleedings, including signed requests from

attending physicians, the donor's disease and disposition of

units.

(v) Immunization, including informed consent, identification

of the antigen, dosage and route of administration.

(vi) Blood collection, including identification of the

phlebotomist.

(2) Processing records:

(i) Blood processing, including results and interpretation

of all tests and retests.

(ii) Component preparation, including all relevant dates and

times.

(iii) Separation and pooling of recovered plasma.

(iv) Centrifugation and pooling of source plasma.

(v) Labeling, including initials of person(s) responsible.

(3) Storage and distribution records:

(i) Distribution and disposition, as appropriate, of blood

and blood products.

(ii) Visual inspection of whole blood and red blood cells

during storage and immediately before distribution.

(iii) Storage temperature, including initialed temperature

recorder charts.

(iv) Reissue, including records of proper temperature

maintenance.

(v) Emergency release of blood, including signature of

requesting physician obtained before or after release.

(4) Compatibility test records:

(i) Results of all compatibility tests, including

crossmatching, testing of patient samples, antibody screening and

identification.

(ii) Results of confirmatory testing.

(5) Quality control records:

(i) Calibration and standardization of equipment.

(ii) Performance checks of equipment and reagents.

(iii) Periodic check on sterile technique.

(iv) Periodic tests of capacity of shipping containers to

maintain proper temperature in transit.

(v) Proficiency test results.

(6) Transfusion reaction reports and complaints, including

records of investigations and followup.

(7) General records:

(i) Sterilization of supplies and reagents prepared within

the facility, including date, time interval, temperature and

mode.

(ii) Responsible personnel.

(iii) Errors and accidents.

(iv) Maintenance records for equipment and general physical

plant.

(v) Supplies and reagents, including name of manufacturer or

supplier, lot numbers, expiration date and date of receipt.

(vi) Disposition of rejected supplies and reagents used in

the collection, processing and compatibility testing of blood and

blood components.

which relates the unit of blood collected to that donor, to his

medical record, to any component or blood product from that

donor's unit of blood, and to all records describing the history

and ultimate disposition of these products.

(d) Records shall be retained for such interval beyond the

expiration date for the blood or blood component as necessary to

facilitate the reporting of any unfavorable clinical reactions.

The retention period shall be no less than 5 years after the

records of processing have been completed or 6 months after the

latest expiration date for the individual product, whichever is a

later date. When there is no expiration date, records shall be

retained indefinitely.

(e) A record shall be available from which unsuitable donors

may be identified so that products from such individuals will not

be distributed.

Section 606.165 Distribution and receipt; procedures and

records.

(a) Distribution and receipt procedures shall include a

system by which the distribution or receipt of each unit can be

readily determined to facilitate its recall, if necessary.

(b) Distribution records shall contain information to

readily facilitate the identification of the name and address of

the consignee, the date and quantity delivered, the lot number of

the unit(s), the date of expiration or the date of collection,

whichever is applicable, or for crossmatched blood and blood

components, the name of the recipient.

the collecting facility, date received, donor or lot number

assigned by the collecting facility and the date of expiration or

the date of collection, whichever is applicable.

Section 606.170 Adverse reaction file.

(a) Records shall be maintained of any reports of complaints

of adverse reactions regarding each unit of blood or blood

product arising as a result of blood collection or transfusion. A

thorough investigation of each reported adverse reaction shall be

made. A written report of the investigation of adverse reactions,

including conclusions and followup, shall be prepared and

maintained as part of the record for that lot or unit of final

product by the collecting or transfusing facility. When it is

determined that the product was at fault in causing a transfusion

reaction, copies of all such written reports shall be forwarded

to and maintained by the manufacturer or collecting facility.

(b) When a complication of blood collection or transfusion

is confirmed to be fatal, the Director, Office of Compliance,

Center for Biologics Evaluation and Research, shall be notified

by telephone or telegraph as soon as possible; a written report

of the investigation shall be submitted to the Director, Office

of Compliance, Center for Biologics Evaluation and Research,

within 7 days after the fatality by the collecting facility in

the event of a donor reaction, or by the facility that performed

the compatibility tests in the event of a transfusion reaction.

(Information collection requirements approved by the Office

of Management and Budget under control number 0910-0116)

[40 FR 53532, Nov. 18, 1975, as amended at 49 FR 23833, June 8,

1984; 50 FR 35471, Aug. 30, 1985; 55 FR 11014, Mar. 26, 1990]