Critical deficiencies of radiopharmaceutical reconstitution and quality control instructions.

Objectives The purpose of this study was to identify deficiencies in package insert instructions for reconstitution and quality control (QC) of radiopharmaceuticals. Focus was placed on deficiencies that would affect the preparation of a safe and quality product.

Methods Preparation instructions, including both reconstitution and QC, were evaluated for all commercially available radiopharmaceuticals as of January 2015. Each package insert was evaluated for deficiencies in the following categories: absent, incomplete, inconsistent, and inaccurate information. Analysis was performed by each contributing author, then compiled and evaluated as a group. The evaluation of each package insert was based on the ability for a certified professional end user to satisfactorily prepare a safe and quality radiopharmaceutical when the instructions were strictly followed. For those package inserts that contained deficiency, the United States Pharmacopeia (USP) monograph was reviewed to determine if it could be an alternative resource.

Results There were 23 deficiencies identified in 29 analyzed package inserts for a total of 20 different reconstituted radiopharmaceuticals. These deficiencies were as follows: 15 (65.2%) absent instructions, 5 (21.7%) incomplete instructions, 1 (4.4%) inconsistent instructions, and 2 (8.7%) inaccurate instructions. Of the absent and incomplete deficiencies, all but one were pertaining to missing QC information. Though USP monograph provides detailed QC information, some QC attributes are impractical (e.g., time-consuming radiochemical purity procedure, biological distribution, and sterility testing).

Conclusions Only six radiopharmaceuticals have the adequate instructions for reconstitution and QC. The majority of package inserts do not have the suitable information which would pose safety and quality concerns to the final products.