Sterile products include: parenterals (injectables), ophthalmics, inhalation aerosols, and their administration devices.

One of the first steps in manufacturing a sterile product is the use of rigid aseptic procedures in a well designed controlled clean room environment. Clean rooms are constructed, and maintained to prevent environmental contamination during manufacture.  Includes: o smooth walls and floors o nonporous (e.g., stainless steel) counters o Clean air - most important component of the clean room o Ultraviolet lights can also be used

How is clean air generated and maintained? i) HEPA (High Efficiency Particulate Air) Filters: Used to filter the air that enters the clean room

 Removes 99.97% of particles 0.3 microns or larger  Considerably reduces, but does not eliminate the chances of contamination

ii) Positive Pressure Filtered air admitted to a sterile area must be of higher pressure than the surrounding areas. This serves to force particles away from the clean room that might be introduced from other incoming areas, such as entry doors, or pass throughs.

Sterilization methods sterilization = complete destruction or removal of living organisms and their spores Physical Methods of Sterilization Methods Conditions Applications/Comments 1. Thermal

Moist (steam) heat 121¨¬C for at least 15 min.

Conducted at high pressure in an autoclave. Economical, fairly low temperatures

Suitable for solutions, glassware, surgical dressings, and instruments

Not suitable for oils, fats, or powders Dry heat 170¨¬C for more than 120 min. For substances not effectively sterilized by moist heat 2. Filtration Retention of particles larger than the rated pore size

(generally 0.22 ¥ìm) Only useful for solutions

Can be used for heat-sensitive products

Removes living and dead organisms and particulates.

Convenient

Possible drug adsorption to the filter material 3. Radiation Gamma-rays Can sterilize contents in sealed packages without heat. UV light (253.7 nm) Does not penetrate packaging well

Used most often as a step in maintaining sterile water systems

Chemical Methods 4. Gas Diluted ethylene or propylene oxide Great penetration through packaging materials

Difficult, time-consuming, & dangerous

3) USP Sterility Tests

Sterility tests must be performed on all sterile products. The focus of these tests is on the absence of bacteria.

Two official (USP) methods: USP <71>

(1) Membrane Filtration (preferred)

(2) Direct transfer of sample to sterile culture media (used for all devices)