Phar 15.36(1)(a)1. 1. Visually inspect the container closure for leakage, cracks in the container, or improper seals.

Phar 15.36(1)(a)2. 2. Visually check the compounded sterile preparation for phase separation.

Phar 15.36(1)(a)3. 3. Each individual injectable unit shall be inspected against a lighted white background and a black background for evidence of visible particulates or other foreign matter or discoloration.

Phar 15.36(1)(b) (b) For compounded sterile preparations which will not be dispensed promptly after preparation, an inspection shall be conducted immediately before it is dispensed for any defects, including precipitation, cloudiness, or leakage, which may develop during storage.

Phar 15.36(1)(c) (c) Compounded sterile preparations with any observed defects shall be immediately discarded or marked and segregated from acceptable units in a manner that prevents them from being dispensed.

Phar 15.36(2) (2) Sterility Testing.

Phar 15.36(2)(a) (a) The membrane filtration method shall be used for sterility testing unless it is not possible due to the compounded sterile preparation formulation. The direct inoculation of the culture method shall be used when the membrane filtration method is not possible.

Phar 15.36(2)(b) (b) If a preparation may be needed before the results of sterility testing have been received, the pharmacy shall daily observe the incubating test specimens and immediately recall the dispensed preparations when there is any evidence of microbial growth in the test specimens. The patient and the prescriber to whom a potentially contaminated compounded sterile preparation was administered shall be notified immediately of the potential risk.

Phar 15.36(2)(c) (c) Positive sterility test results shall prompt a rapid and systematic investigation into the causes of the sterility failure, including identification of the contaminating organism and any aspects of the facility, process or personnel that may have contributed to the sterility failure. The investigation and resulting corrective actions shall be documented.

Phar 15.36(2)(d) (d) All Category 2 compounded sterile preparations made from one or more nonsterile ingredients, except those for inhalation and ophthalmic administration, shall be tested to ensure that they do not contain excessive bacterial endotoxins.

Phar 15.36(2)(e) (e) Notwithstanding par. (d), a compounded sterile preparation does not need to be tested for bacterial endotoxins if the material is stored under cool and dry conditions and one of the following:

Phar 15.36(2)(e)1. 1. The certificate of analysis for the nonsterile ingredient lists the endotoxins burden, and that burden is found acceptable.

Phar 15.36(2)(e)2. 2. The pharmacy has predetermined the endotoxins burden of the nonsterile ingredient and that burden is found acceptable.

Phar 15.36(3) (3) Antimicrobial effectiveness. Compounded sterile preparations containing a preservative added by the compounder shall pass an antimicrobial effectiveness testing with the results obtained on the specific formulation before any of the compounded sterile preparation is dispensed. The test may be conducted only once on each formulation in the particular container-closure system in which it will be stored or dispensed. The antimicrobial effectiveness test shall occur at one of the following times:

Phar 15.36(3)(a) (a) At the completion of the sterility test.

Phar 15.36(3)(b) (b) At the time of preparation for compounded sterile preparations which have not undergone a sterility testing.

Phar 15.36 History History: CR 16-085: cr. Register April 2018 No. 748 eff. 11-1-18.

Phar 15.37 Phar 15.37 Beyond use dating.

Phar 15.37(1) (1) Sterility and stability considerations shall be taken into account when establishing a BUD. Either Category 1 and 2, or low, medium, and high-risk compounding preparation standards may be used, but not a combination of the two within the same pharmacy. The following dates and times for storage and initiation of administration of the compounded sterile preparations shall apply:

Phar 15.37(1)(a) (a) For compounded sterile preparations including components from conventionally manufactured products, the BUD shall not exceed the shortest expiration of any of the starting components. If the compounded sterile preparation includes non-conventionally manufactured products, the BUD may not exceed the shortest BUD of any of the starting components.

Phar 15.37(1)(b) (b) For Category 1 compounded sterile preparations, one of the following:

Phar 15.37(1)(b)1. 1. May not exceed 12 hours when the preparation is stored at controlled room temperature.

Phar 15.37(1)(b)2. 2. May not exceed 24 hours when the preparation is stored in a refrigerator.

Phar 15.37(1)(c) (c) For aseptically processed Category 2 processed sterile preparations, one of the following:

Phar 15.37(1)(c)1. 1. No sterility testing performed or sterility testing not passed, and prepared with one or more nonsterile starting components, one of the following:

Phar 15.37(1)(c)1.a. a. Within 1 day when the preparation is stored at controlled room temperature.

Phar 15.37(1)(c)1.b. b. Within 4 days when the preparation is stored in a refrigerator.

Phar 15.37(1)(c)1.c. c. Within 45 days when the preparation is stored in a freezer.

Phar 15.37(1)(c)2. 2. No sterility testing performed or sterility testing not passed, and prepared with only sterile starting components, one of the following: