Expiration date for a 6% solution of albumin made from a commercially prepared 22% solution of albumin

A transfusion service lead technologist located in Nevada asks if colleagues would comment upon what they use as an expiration date for a 6% solution of albumin made from a commercially prepared 22% solution of albumin, when the 22% albumin has been diluted with 0.8% saline. She states that Method 1.5 on pages 726 and 727 of the 15th edition of the AABB Technical Manual discusses the procedure to accomplish this dilution, but gives no guidance as to the expiration date of the newly prepared diluted solution. Furthermore, the cited references for this method (on page 728) are quite old. She acknowledges not having checked these references to determine if an expiration recommendation is given. She attempted to contact the manufacturer of the 22% albumin to ascertain if they can be of help in this matter, but they merely told her to check the old references given in the Technical Manualor to perform an in-house validation of the diluted product. However, the inquiring colleague points out that since this diluted product is utilized as a negative control, she is not certain how she can determine if it is performing as expected, given no visible cloudiness or contamination are observed? In the meantime, she is interested in input from other blood bank professionals.

The following comments have been received.

ADDENDA October 2, 2007

1. A colleague affiliated with an immunohematology reference laboratory reports that it is important to check the reagent manufacturer's instructions as some have a statement regarding not diluting their reagent. So assuming that the manufacturer is silent about dilution, then the lab can proceed. The best choice is to validate newly prepared reagent versus stored reagent using boundary testing scenarios. If the laboratory has not "validated" the storage time and determines it cannot, then reasonable choices should be made. Assignment of expiration date could be based on historical information (retrospective review) that there were no adverse impacts of storage of the solution in a variety of cases. It is impossible to be able to give a standard time without knowledge of the use and storage parameters of the reagent. It is also important to have the practice and validation process approved by the facility's Quality Assurance Unit (or its equivalent).

ADDENDA October 4, 2007

2. A colleague who works in an Immunohematology Reference Laboratory located in Southern California reports that they prepare 6% and 10% albumin from commercial sources of albumin (22% is now all that is available) using a method similar to that cited from the Technical Manual. They use a 6-month expiration date because that has worked successfully for them for many years, but they occasionally use up the preparation before 6 months has elapsed. Like the manufacturer recommends, each lab would have to determine by day-of-use QC whether the in-house preparation is working as expected up to the projected expiration date. The obvious risk in this instance is contamination of the reagent, so her advice would be to prepare an amount that would last a few months and aliquot it into smaller vials so that if one vial got contaminated, another vial would be available to use if additional reagent needed to be prepared. As for the comment regarding manufacturer’s directions not to dilute the reagent, they asked an FDA representative (speaker at a conference) about this exact situation. Her response was that the manufacturer’s warning applied to use of that reagent for the purpose of antibody enhancement (e.g., antibody screening or identification) but that if the 22% albumin were just being used as a source of albumin for a totally different purpose, the manufacturer’s warning did not apply.
   
   
3. An immunohematology specialist and an associate editor of the 16th edition of the AABB Technical Manual reports that at her hospital, they use a commercially prepared saline that has an expiration of 30 days from the date of opening. When preparing reagents using this saline they assign an outdate based on the shortest outdate of all the components; this usually ends up being the outdate of the saline. When saline prepared in-house is used and the albumin has an outdate 12 or more months in the future, using the outdate of the albumin may not be appropriate. In this situation, validation should be done for a reasonable outdate such as 1-3 months. Although this reagent is used as a negative control, validation of expected negative results and lack of visible contamination can be performed. Finally, she points out to the colleague who initiated this discussion that in the 15th edition of the AABB Technical Manual, there are no references associated with Method 1.5 Dilution of % Solutions. The cited references on page 728 are with Method 1.7 Preparation and Use of Phosphate Buffer.

ADDENDA Oct. 23, 2007

4. A technical supervisor at a transfusion service in an Arizona hospital reports that they prepare 6% albumin by combining 36.6 ml of normal saline with 10 ml of 22% albumin. They label the diluted reagent with "No Expiration Date" and use the 6% albumin as long as 'QC' is acceptable. The QC consists of testing the 6% albumin against a reagent red cell used for patient testing to obtain an expected negative result. She comments that colleagues who impose a 30 day expiration for diluted albumin reagent seem to be doing so based on the expiration of room temperature stored saline used in the dilution step. Since the Arizona colleague's lab stores their 6% albumin at refrigerator temperature, they do not believe that a 30 day expiration is applicable. Finally, it has been their experience that by preparing 10 ml of 6% albumin at a time, they use up the reagent before any contaminant has a chance to grow.
   
   
5. Editors' note: The current CAP transfusion medicine checklist (available online from CAP.org) includes Phase II item TRM.31220: Are reagents and solutions properly labeled, as applicable and appropriate, with the following elements?
   1. Content and quantity, concentration or titer
   2. Storage requirements
   3. Date prepared or reconstituted by laboratory
   4. Expiration date
   5. Lot number, as applicable

The previous e-Network Forum discussion "What are the QC requirements for isotonic saline used with automatic cell washers?" may be germane to this topic.

6. Editors' note: 42 CFR 493.1252(b) appears to be germane to this topic and is reproduced below:

The laboratory must define criteria for those conditions that are essential for proper storage of reagents and specimens, accurate and reliable test system operation, and test result reporting. The criteria must be consistent with the manufacturer's instructions, if provided. These conditions must be monitored and documented and, if applicable, include the following:

(1) Water quality.
(2) Temperature.
(3) Humidity.
(4) Protection of equipment and instruments from fluctuations and interruptions in electrical current that adversely affect patient test results and test reports.

(c) Reagents, solutions, culture media, control materials, calibration materials, and other supplies, as appropriate, must be labeled to indicate the following:

(1) Identity and when significant, titer, strength or concentration.
(2) Storage requirements.
(3) Preparation and expiration dates.
(4) Other pertinent information required for proper use.

(d) Reagents, solutions, culture media, control materials, calibration materials, and other supplies must not be used when they have exceeded their expiration date, have deteriorated, or are of substandard quality.
(e) Components of reagent kits of different lot numbers must not be interchanged unless otherwise specified by the manufacturer.

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