Phar 15.35(3)(b)1.1. All materials shall be directly exposed to steam under adequate pressure for the length of time necessary, as determined by use of appropriate biological indicators, to render the items sterile. The duration of the exposure period shall include sufficient time for the compounded sterile preparation to reach the sterilizing temperature.

Phar 15.35(3)(b)2.2. The compounded sterile preparation and other items shall remain at the sterilizing temperature for the duration of the sterilization period. The sterilization cycle shall be designed to achieve a sterility assurance level of 10-6.

Phar 15.35(3)(b)3.3. Compounded sterile preparations shall be placed in trays which allow steam to reach the compounded sterile preparations without entrapment of air. Paper, glass, and metal devices or items shall be wrapped in low lint protective fabric, paper, or sealed in envelopes that will permit steam penetration and prevent post sterilization microbial contamination.

Phar 15.35(3)(b)4.4. Immediately before filling ampules and vials, solutions shall be passed through a filter having a nominal pore size of not larger than 1.2 microns for removal of particulate matter.

Phar 15.35(3)(b)5.5. Sealed containers shall be able to generate steam internally. Stoppered and crimped empty vials shall contain a small amount of moisture to generate steam. Deep containers, including beakers and graduated cylinders, shall be placed on their sides to prevent air entrapment or have a small amount of water placed in them.

Phar 15.35(3)(b)6.6. Porous materials and items with occluded pathways shall only be sterilized by steam if the autoclave chamber has cycles for dry goods.

Phar 15.35(3)(b)8.8. The seals on the doors of autoclave chambers shall be examined visually every day they are used for cracks or damage and the seal surfaces shall be kept clean.

Phar 15.35(3)(b)9.9. A data recorder or chart shall be used to monitor each cycle and the data shall be reviewed to identify cycle irregularities in temperature or exposure time.

Phar 15.35(3)(b)10.10. Materials in direct contact with the compounded sterile preparation shall undergo a depyrogenation process before being sterilized using steam heat unless the materials used are certified to be pyrogen-free.

Phar 15.35(3)(c)(c) Sterilization by dry heat. Dry heat sterilization shall be used only for those materials that cannot be sterilized by steam or filtration. The effectiveness of dry heat sterilization shall be verified using appropriate biological indicators and temperature sensing devices. This method shall meet all of the following:

Phar 15.35(3)(c)1.1. The duration of the exposure period shall include sufficient time for the compounding sterile preparation or items to reach the sterilizing temperature. The compounded sterile preparation and items shall remain at the sterilizing temperature for the duration of the sterilization period.

Phar 15.35(3)(c)3.3. Sufficient space shall be left between materials to allow for good circulation of the hot air.

Phar 15.35(3)(c)5.5. A data recorder or chart shall be used to monitor each cycle and the data shall be reviewed to identify cycle irregularities in temperature or exposure time.

Phar 15.35(3)(c)6.6. Materials shall first undergo a depyrogenation process before being sterilized using dry heat, unless the materials used are certified to be pyrogen-free.

Phar 15.35(4)(4) Dry heat depyrogenation shall be used to render glassware and other thermostable containers pyrogen free. The duration of the exposure period shall include sufficient time for the items to reach the depyrogenation temperature. The items shall remain at the depyrogenation temperature for the duration of the depyrogenation period. The effectiveness of the dry heat depyrogenation cycle shall be established and verified annually using endotoxin challenge vials to demonstrate that the cycle is capable of achieving at least a 3-log reduction in endotoxins.

Phar 15.36(1)(1) Physical inspection.

Phar 15.36(1)(a)(a) At the completion of compounding, the compounded sterile preparation shall be inspected by performing all of the following:

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)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.