A forum member who lives in Calgary, Alberta (Canada) and who manages an inventory of clotting factor concentrates for the local Hemophilia Clinic is seeking input from the e-network forum. The local Hemophilia Clinic dispenses clotting factor concentrates to patients for storage and use at home, and occasionally a patient returns unused products to the clinic. Due to the high cost and limited availability of these clotting factor concentrates, the returned products are placed back into the inventory, provided there has been no tampering with the product vials. In addition, before being placed back into inventory, a Hemophilia Clinic nurse must sign a disclaimer attesting that the products were stored under proper conditions. However, the inquiring member is skeptical that 100% compliance is always achieved. He asks the e-network if the clinic should continue dispensing clotting factor concentrates that have been returned unused. Do members of the forum think it is unsafe to re-issue these products? If e-network members think it is safe to re-issue these products, what should the proper outdate be for the product vials? Should the outdating be based on products stored at 2-6 C, or should the outdating be based on the products stored at room temperature?

The following replies were submitted:

1. A blood banker from Northwestern United States commented that his facility re-issues products that have been returned by a reliable patient, provided the expiration date noted on the package has not passed, and the facility personnel are certain that the product was properly stored by the patient. According to the responding member, the clotting factor concentrates in question are products that can be at stored at room temperature for up to 6 months or longer. In fact, the package insert may state that the product can be stored under refrigeration [2° - 8°C (36° - 46°F)] or at room temperature, not to exceed 30°C (86°F), until the expiration date noted on the package. It is important to avoid freezing to prevent damage to the diluent bottle. The responding member shared his belief that the FDA has given approval for some products to be held at room temperature for 30 months (Hemofil M) (Baxter). In the responding member's opinion, a few products are more heat-labile, such as Kogenate® FS (also Bayer web site), and Helixate® FS (ZLB Behring web site ), so it may not be advisable to return these products to the inventory if storage by the patient is of concern. According to the responding member, tampering is the biggest risk to the product's integrity.

2. A blood banker from New York wrote that NY State law PROHIBITS prescription drugs from being returned once they are in the possession of the patient. On the other hand, if a wholesaler or a pharmacy dispenses a product to an institution (i.e., a hospital or nursing home), the product may be returned provided it has not been opened, it shows no signs of deterioration, the packaging has not been adulterated, the product is within its expiration date, and the product has been stored under proper conditions. Policy and procedures must be established prior to the return of products. At the responding member's blood center, they have a declaration statement that each facility must sign before credit is issued. The statement guarantees to the donor center that the facility returning the product has maintained the clotting factors under optimum condition, and the packaging has not been adulterated.

3. A blood banker in California commented that clotting factor concentrates are too expensive to waste. In his opinion, if there is concern about the storage temperature at which these products are maintained, assume the products were kept at room temperature and use the outdate based on room temperature storage. The responding blood banker's donor center verifies that these products have been properly stored by their customer hospitals. If the donor center cannot be assured of proper storage (and an audit of product storage by the hospital customers is done periodically), the donor center does not take components back and does not offer a credit for them.

4. Another blood bankerfrom the Northwestern U.S. commented that the issue under discussion appears not to address the question of regulatory requirements for clotting factor storage, but rather the practical question of the stability of the lyophilized concentrates under unknown storage conditions. The lyophilized proteins are pretty stable even at room temperature, so as a practical question, there shouldn't be too much worry about loss of activity at temperatures between 2 and 20 degrees C. But of course, it depends on how long, and what the storage temperature really was. A few weeks would not likely be any problem, a year at room temperature in a warm climate may be a different matter.

5. Keeping in mind that clotting factor concentrates are dispensed from pharmacies as well as from blood banks, a clinical pharmacist was asked for his opinion. This clinical pharmacist, who practices in Los Angeles, commented that he does not believe that any reasonable pharmacist would ever accept back product from a patient and dispense to someone else. Once it has left the pharmacist's hand there is no way of telling what has happened to the product.

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